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Volume 272, Number 52, Issue of December 26, 1997
pp. 32715-32718
From the Center for Macromolecular Design, the Department of
Biochemistry and Biophysics, and the Department of Chemistry, Texas A&M
University, College Station, Texas 77843-2128
INTRODUCTION The problem of how the linear amino acid
sequence of a polypeptide folds to assume its unique tertiary structure
is one of the most basic and challenging conundrums of contemporary
science. Many of the principles and characteristics of protein folding have been learned by studying refolding of denatured polypeptides. However, the problem of protein folding cannot be completely understood without reference to the biological context of protein folding, especially for large, multidomain, and multisubunit proteins. One of
the basic differences between biosynthetic protein folding and protein
renaturation is cotranslational folding, folding that occurs
during synthesis. The elegant idea that the process of protein folding is concomitant with synthesis was articulated, and
experimental testing was begun in the early 1960s (1, 2). Today there
is substantial experimental support for the cotranslational folding
hypothesis. Both cotranslational and cotranslocational folding, at
least when the latter is coupled to translation, share the basic
feature of vectorial appearance of the nascent polypeptide from the
ribosome or the membrane and the potential initiation of the folding
process by the emerging polypeptide. It is true that the same
conformations are achieved by polypeptides folded in cells as a
consequence of biosynthetic processes and as a result of refolding of
the full-length polypeptide from the denatured state. However, identity
of the final protein structures does not necessarily mean identity of
the pathways leading to their formation (3). It is the kinetics of the
folding process that establishes the folding pathway(s) and potential
partitioning among different final forms and, ultimately, their
relative yields. In fact, the biological function that is shared by all
proteins is the ability to fold properly, and this function must be
executed efficiently by all proteins prior to any other function. This seems to be the essence of the vectorial folding process. Several general patterns and principles of cotranslational folding are summarized in Figs. 1 and
2.
[View Larger Version of this Image (19K GIF file)]
[View Larger Version of this Image (37K GIF file)]
Steps of Protein Folding That Can Occur Cotranslationally Early Stages of Folding Studies of disulfide bond formation in nascent polypeptides have
provided an informative probe of the folding process, since formation
of disulfide bonds reflects acquisition of certain tertiary interactions by the polypeptide. Immunoglobin light chains are two-domain polypeptides with two intramolecular disulfide bonds, one in
the N-terminal domain and the other in the C-terminal domain. Nascent
light chain polypeptides fold in the lumen of the endoplasmic reticulum. The disulfide bond between Cys-35 and Cys-100 of the N-terminal domain starts to form when the nascent chains achieve 15.5 kDa length (8). Formation of this bond is almost quantitative when the
nascent polypeptide has achieved a length of 18 kDa; formation of the
disulfide thus requires ~3 s.
It has been shown with a conformation-dependent antibody
that Escherichia coli tryptophan synthase Binding of Cofactors and Ligands Later Stages of the Folding Process and Formation of
Oligomeric Structures Formation of oligomeric structures involving nascent polypeptides has
been reported for several proteins. Formation of the Cotranslational trimerization of the reovirus cell attachment protein
via the N-terminal domain has been observed, possibly reflecting
trimerization of nascent chains synthesized from adjacent ribosomes in
the same polyribosomal complex (26). The human protein hexabrachion, a
hexamer composed of 320-kDa subunits, achieves its folded form upon
secretion so efficiently that no intermediate forms involving
full-length subunits could be detected in vivo (27). Nascent
polypeptides of several eucaryotic cytoskeletal proteins have been
shown to assemble into the corresponding polymeric cytoskeletal
structures (28).
Formation of the initial complex between immunoglobulin heavy and light
chains involves disulfide bond formation between fully synthesized
light chains and nascent heavy chains (29). The Cys residue from the
heavy chain that is involved in the disulfide bond is located between
two domains, each of which contains a single intradomain disulfide
bridge. It appears that formation of this disulfide bridge requires
prior folding of two adjacent domains.
An intriguing case of cotranslational assembly involves formation of
type I procollagen trimer. Association of full-length chains is
initiated by interactions between C-terminal propeptides (30). The
triple helix propagates from the C-terminal propeptide to the
N-terminal end. In vivo, a substantial portion of nascent collagen is full-length (31) as a consequence of a pause in translation
prior to termination. These fully elongated chains potentially can
associate through their propeptides to provide helix growth from the C
terminus to the N terminus similar to that for the full-length
procollagen. Based on the enhanced stability of the collagen trimer to
proteolysis, it has been suggested that the initial stages of trimer
formation can occur with the nascent collagen chains (32).
Molecular Chaperones and Folding Catalysts in Cotranslational
Folding Chaperones HSP 70 Two members of the HSP 70 family in yeast cells, Ssb1p and Ssb2p, have
been found to interact with nascent polypeptides on translating
ribosomes (37). The defective phenotype of these mutant strains, which
have lower levels of polyribosomes, can be suppressed by
increased expression of the HBS1 gene, which encodes a
polypeptide resembling in sequence the eucaryotic translation elongation factor EF-1 Interaction of nascent rhodanese with DnaK and DnaJ in the E. coli expression system has been studied in some detail. It appears that DnaJ interacts with the nascent polypeptide first, followed by
DnaK, and finally, association of GrpE leads to dissociation of the
complex (40). Interestingly, the nascent rhodanese polypeptide itself
appears to block translation termination and release of the polypeptide
from the ribosome, presumably by interference of the N-terminal segment
of the polypeptide with binding of the translation termination factor
RF2 (41). Binding of this N-terminal segment to the ribosome is only
disrupted by DnaJ in conjunction with DnaK (40, 42). Accumulation of
the ribosome-bound full-length polypeptide on the ribosome due to
impeded termination is not prevented by the endogenous
chaperones; release requires incubation with chaperones at high
concentration (41).
HSP 60 An important question has been raised concerning the fraction of
cellular proteins assisted by chaperones in folding. It has been
estimated that no more than 5% of the polypeptides in E. coli fold with the assistance of GroE (44). In this regard, it
should be remembered that rhodanese and firefly luciferase are
translocated proteins that fold in an environment different from
that of the cytoplasm and generally do not refold spontaneously without
the aid of chaperones. It would be premature to extrapolate the
requirements of chaperones found for folding of these proteins to all
proteins.
Some other chaperones have been implicated in binding nascent chains of
particular groups of proteins. SecB can bind nascent polypeptides of
E. coli secretory proteins, apparently preventing premature
folding in the cytoplasm (46). Calnexin, a chaperone in the endoplasmic
reticulum membrane, binds transiently to some glycoproteins and is
required for their proper folding and assembly. It has been found to
bind hemagglutinin nascent chains via oligosaccharides attached to the
polypeptide (18). Another chaperone from the same cellular compartment,
HSP 47, associates with nascent procollagen (47). Inactivation of HSP
47 leads to reduced synthesis of collagen and delay in its folding.
Folding Catalysts Ribosomes Kinetics and Pathway of Cotranslational Folding An upper limit of the rate of cotranslational folding is imposed
by the rate of polypeptide synthesis. For many proteins, as mentioned
above, the C-terminal segment of 20-30 amino acid residues, which is
sheltered by the ribosome prior to the release of the full-length
polypeptide into the bulk solution, is essential for formation of the
native, biologically active structure. Consequently, folding cannot be
completed before release of the nascent polypeptide from the ribosome.
The kinetics of folding of the polypeptide and ultimate appearance of
the native form will be a function of the rates of polypeptide
synthesis, folding of the full-length monomer, and for oligomeric
proteins, subunit assembly. Manipulation of the conditions of protein
expression can change the rate-limiting step of the folding/association
process and, consequently, change the kinetics of the overall process.
For oligomeric proteins, the concentration of newly synthesized
monomers is critically important because the association reaction is a
higher order, concentration-dependent process. Cotranslational
folding of the bacterial luciferase For many proteins for which folding events have been observed with
nascent chains, cotranslational processes may contribute to the fast
rate of biosynthetic folding. The rapid rates of biosynthetic folding
cannot be achieved upon renaturation of denatured full-length polypeptides in the presence of chaperones and folding catalysts. The
point of concern in the investigation of folding of ribosome-bound chains has been the possibility that rather slow folding events might
occur during the time required for analysis of the ribosomal complexes.
However, in several cases, late folding events which occur
cotranslationally in vivo, or in vitro prior to
analysis, have been observed. Biosynthetic folding seems to be much
faster and more efficient than renaturation for several proteins (Refs. 8, 18, 20, 25, 29, 30, and references therein). Firefly luciferase (57)
and hydroid obelin2 fold much
more efficiently during synthesis than during renaturation under the
same conditions. Firefly luciferase also folds efficiently upon
translocation into proteoliposomes depleted of chaperones (58). These
observations imply a crucial role for vectorial folding of nascent
chains.
The time course of biosynthetic folding relative to renaturation has
been compared directly for bacterial luciferase (55), a cytoplasmic
protein that contains no disulfide bonds. Isomerization of prolyl
residues is not rate-limiting in its folding, at least in the refolding
of full-length subunits. Association of The significance of vectorial folding to the kinetics of polypeptide
synthesis has been tested using permuted proteins. It has been
established that some permuted polypeptides can fold and acquire native
structure. However, as discussed above, the basic parameters that can
be determined by cotranslational folding are kinetics and efficiency of
the folding process. Indeed, analysis of the kinetics of refolding of
permuted versions of ribonuclease T1 and Statistical analysis of more than 200 protein structures has revealed
the tendency that, within the length of polypeptide typical for a
domain, residues tend to interact with the N-terminal portion of the
polypeptide and that the N-terminal region is, on average, more compact
than the C-terminal region (62). This observation is consistent with
vectorial folding of nascent polypeptides beginning from the N terminus
and proceeding to the C terminus.
Conclusions and Perspectives In this review, we have tried to demonstrate that cotranslational
folding is an essential component of biosynthetic folding of many
proteins in cells. This stage of folding may be crucial for the overall
kinetics and yield of folding. Cotranslational folding appears to be
especially important for large multidomain and multisubunit proteins.
Indeed, all proteins discussed in the review fall into this category.
The ultimate goal of studies of cotranslational protein folding is to
learn the details of the pathways involved. The kinetics of the folding
process, the partitioning of polypeptides among alternative forms, and
the yield of correctly folded protein are consequences of kinetic
partitioning between alternative pathways. The basic differences
between cotranslational folding and the refolding of the full-length
polypeptide are: 1) vectorial appearance of the nascent polypeptide and
subsequent vectorial folding which decreases the potential for
nonproductive interactions and allows folding by consecutive parts; 2)
isomerizations within the partially folded N-terminal segment of a
polypeptide which occur concomitantly with the synthesis of the
C-terminal segment of the polypeptide; 3) restricted diffusion and
attachment of the nascent chain to the large ribosomal particle, which
reduces the aggregation potential of the nascent polypeptides; 4)
formation of disulfide bonds and proper prolyl isomer conformation,
which may be catalyzed more efficiently prior to formation of
structural intermediates in which the Cys and Pro residues are not
accessible for the PDI and PPI.
Recently it has been suggested that eucaryotic proteins fold
cotranslationally whereas procaryotic proteins fold posttranslationally and that some components of bacterial cells prevent folding of nascent
polypeptide chains (63). Demonstration of cotranslational folding of
procaryotic proteins in bacterial cells and extracts (1, 2, 9, 10-12,
55) and of folding of ribosome-bound eucaryotic proteins in bacterial
systems (14-16, 22) clearly contradicts this proposal.
The involvement of chaperones in cotranslational folding of specific
proteins may be the basis of the multiple effects apparently exerted by
chaperones on the folding process. These include decreasing aggregation
by binding aggregation-prone intermediates, potential unfolding of
nonproductive folding intermediates, and assisting the polypeptide in
overcoming energy barriers in the folding reaction (33, 35). It remains
to be ascertained which nascent polypeptides are targets for chaperones
and folding catalysts and to learn the details of their action.
Both experimental and theoretical studies of protein refolding suggest
that there is evolutionary pressure for proteins to fold fast (5, 64,
65). Folding of larger proteins generally involves smaller independent
folding units (64, 65). We believe that the evolutionary pressure for
fast folding operates in the context of biosynthetic folding, including
vectorial synthesis and concomitant folding of the nascent polypeptide
chain, obviously not on refolding of the full-length polypeptide.
FOOTNOTES ACKNOWLEDGEMENTS We are deeply indebted to our colleagues who
supplied us with reprints and manuscripts. We are especially grateful
to Profs. Ken Dill and Peter Wolynes for their discussion of Fig. 2. We also apologize to our colleagues whose work could not be cited due to
space limitations; we recognize that our conclusions are based on the
efforts of many. We thank Dr. Paul Swartz for assistance with the
figures and Dr. Miriam M. Ziegler for many thought-provoking discussions and for assistance with the manuscript.
REFERENCES
MINIREVIEW:
Cotranslational Protein Folding*
INTRODUCTION
Steps of Protein Folding That Can Occur Cotranslationally
Molecular Chaperones and Folding Catalysts in Cotranslational
Folding
Kinetics and Pathway of Cotranslational Folding
Conclusions and Perspectives
FOOTNOTES
ACKNOWLEDGEMENTS
REFERENCES
Fig. 1.
Cartoon depiction of cotranslational folding
of a polypeptide. The nascent polypeptide is shown assuming
secondary structure as it emerges from the ribosome during the process
of biosynthesis. The earliest intermediate, I1,
is not well-stabilized by extensive tertiary interactions and is in
equilibrium with multiple conformations. The second intermediate shown,
I2, is the N-terminal domain; more extensive
tertiary interactions will allow this intermediate to be more stable.
The final intermediate, I3, depicts the
structure of the full-length polypeptide immediately prior to release
from the ribosome with the C-terminal domain not yet fully packed.
Chaperones and/or folding catalysts (CH and FC)
may interact with either the nascent intermediate structures or with
the full-length product (M*) following release from the ribosome. The final stages of folding from M* to native
monomer, Mn, occur following release. Association of
monomeric units into oligomeric structures, O, may occur
posttranslationally as depicted or, as discussed in the text, may
involve nascent polypeptides. The structure that was used to develop
this cartoon was of one subunit of the bacterial luciferase
2 homodimer (66).
Fig. 2.
Schematic representation of a section through
a protein folding landscape in which the basic funnel concept described
by others for refolding polypeptides (67, 68) has been adapted to
include the processes of cotranslational folding. The energy surface on the left depicts the hypothetical case of protein
biosynthesis in the absence of folding (blue
arrows). The vertical axis represents conformational energy of the
polypeptide, whereas the circumference of the funnel represents the
conformational space available to the polypeptide. As the polypeptide
emerges from the ribosome, the available conformations will increase
(the funnel becomes wider) as the length of the polypeptide increases,
and as the polypeptide emerges into the aqueous environment but does
not fold, it will move up the surface of the funnel to higher energies. The blue surface represents processes involving covalent
bond formation and hydrolysis; the overall process of biosynthesis and
folding constitutes movement from left to right.
The green surface represents noncovalent interactions
associated with protein folding. When the full-length but still
unfolded polypeptide is released from the ribosome, it will be free to
fold to the native state through the pathways defined by the folding
funnel on the right (green arrows). The more
realistic model of cotranslational folding is viewed as a tunneling
process whereby the nascent polypeptide folds through a series of
intermediates as it emerges from the ribosome, thereby retaining a
lower energy than would be the case for synthesis without folding. The
nascent polypeptide at each stage of biosynthesis will be able to
access multiple conformations thus defining a folding funnel similar to
that of the full-length polypeptide on the right; we have
simplified the figure by showing the most highly populated species at
each step of synthesis in the form of a tunnel. When sufficient
polypeptide has emerged to begin to assume some structure, we envision
the biosynthesis/folding process as leaving the blue funnel
and "tunneling" to the folding (green) funnel. The
intermediates I1, I2, and
I3 are as defined in the legend to Fig. 1. The
position on the biosynthesis funnel at which the tunnel begins reflects
the length of nascent polypeptide required to stabilize a subset of
conformational states; the different tunnels were included to indicate
that some polypeptides may require longer N-terminal sequences before
any structures become stabilized. The full-length nascent polypeptide,
M* folds to native monomer, Mn, following
release by packing of the C-terminal segment of polypeptide and final
isomerization steps. Note that the cotranslational folding pathway
maintains a lower barrier than would occur with synthesis in the
absence of folding and therefore would be expected to occur faster. It
also appears that cotranslational folding would allow the polypeptide
to avoid kinetic traps that may be encountered during refolding of
full-length polypeptides.
Early stages of protein
folding proceed quickly; secondary structure formation and compaction
require much less then 1 s (4). Formation of compact globular
intermediates usually requires no more then a few seconds (5).
Since polypeptide synthesis requires many seconds (50-300 residues/min
for cell-free systems and somewhat faster in vivo; see Ref.
6 and references therein), compact intermediates must be formed in the
process of synthesis. Stereochemical analysis suggests that the nascent polypeptide emerges from the peptidyltransferase center in an 
-helical configuration (7).
chains begin
to fold during translation, even before appearance of the entire
N-terminal domain (9, 10). No lag was detected between synthesis of the
nascent chains and appearance of immunoreactivity (11). Monoclonal antibody recognizing the structured monomer of bacteriophage P22 tailspike protein reacts with nascent chains (12). Ribosome-bound firefly luciferase and bovine rhodanese form protease-resistant N-terminal domains (13, 14). Folding of ribosome-bound rhodanese and of
ricin has been observed through the use of fluorescent probes (15,
16).
Binding of cofactors
and ligands often stabilizes protein structure and can affect folding pathways. For the chloroplast reaction center protein D1, binding of
several cofactors has been found to occur during synthesis and
translocation into the thylakoid membrane (17). Cotranslational binding
of chlorophyll is required to synthesize the full-length protein and
prevent degradation of the nascent chains. Glycosylation of influenza
hemagglutinin occurs in the lumen of the endoplasmic reticulum (18).
Upon blockage of oligosaccharide addition, folding of the protein is
perturbed, leading to the formation of aggregates. Binding of heme to
rabbit -globin begins when the emerging polypeptide achieves a
length of 86 residues (19). Attachment of ligands and cofactors in all
the above cases can occur immediately upon or very soon after
appearance of the binding sites along the polypeptide chain, thereby
stabilizing the tertiary structure of the nascent polypeptide.
Rat serum albumin is a secretory protein
with 17 disulfide bonds in the native structure which are spread
throughout the polypeptide chain. In the nascent polypeptides, about
one-half of the cysteinyl residues exist in disulfide bonds, indicating completion of a substantial part of the overall folding process (20).
Hemagglutinin-neuraminidase of Newcastle disease virus begins to assume
defined structure during the process of synthesis (21). Nascent
influenza hemagglutinin also forms disulfide bonds cotranslationally,
including the critically important 52-277 bond (18). Two recent
studies have demonstrated formation of enzymatically active forms
of rhodanese and firefly luciferase still bound to the ribosomes when
these polypeptides are expressed with extended C-terminal segments so
that each enzyme was in the bulk solution (22, 23). Polyribosomes from
Chironomus salivary gland cells produce giant secretory
proteins having compact domain-like structures (24).
-galactosidase
oligomer from nascent polypeptides was suggested in the pioneering
studies of cotranslational folding. Ribosome-bound -galactosidase
chains can complement functionally defective subunits and produce
ribosome-bound enzymatically active forms upon coexpression in
heterozygous strains of E. coli or by mixing subunits
in vitro (1). Formation of enzymatically active
-galactosidase on ribosomes also was observed following enzyme
induction in vivo (2). The modular organization of the
monomer and independent folding of each domain provides an explanation
for how this large tetrameric complex could be formed with one monomer
not yet completely synthesized (25). The authors suggested the
possibility of formation of a dimeric complex between nascent
polypeptides attached to neighboring ribosomes and then, by a similar
mechanism, formation of the tetramer (2).
Molecular chaperones are ubiquitous
components of cells. In the presence of co-chaperones and ATP,
substrate polypeptides form transient complexes with chaperones,
cycling between free and chaperone-bound forms (33), leading to
competition between folding polypeptides for binding to the chaperones
(34). The binding affinity of substrate polypeptides to chaperones in
the absence of ATP is substantially higher (by orders of magnitude), and dissociation of the complexes is extremely slow (33, 35).
Members of the HSP 70 chaperone family include
DnaK and DnaJ in procaryotic cells and eucaryotic HSP 70 and its
co-chaperone HSP 40. When polyribosomal complexes consisting of the
entire spectrum of nascent polypeptides were analyzed, it was shown
that HSP 70 chaperones were associated with the nascent
polypeptides (36-38). Some chaperones associated with the
ribosomes may be involved in the translation process itself (39).
and translation termination factor (37).
Studies of the potential involvement of HSP 60 in cotranslational folding have yielded controversial results because of the difficulty in distinguishing between interactions of the chaperone with nascent polypeptides from interactions with polypeptides immediately after release into the bulk solution. Exposure of the
C-terminal segment of 20-30 amino acid residues, which are sheltered
within the ribosome during synthesis, can change the folding properties
of the released polypeptide as well as its interactions with
chaperones. GroE is required to produce rhodanese in an enzymatically
active form during synthesis (41). Similar results have been obtained
for TRiC, a mammalian cytoplasmic member of the HSP 60 family, for
synthesis of firefly luciferase and of actin (13, 43). Clearly, these
experiments, while demonstrating a requirement of HSP 60 for productive
folding of these polypeptides, do not inform us of whether the
interaction occurs during synthesis or after release of the polypeptide
from the ribosome. The C-terminal sequences of firefly luciferase and
actin are critical for binding of the polypeptides to TRiC (13, 43).
There is a huge excess of endogenous chaperones, 2.6 µM
GroE (44) and 1 µM TRiC (13), over nascent polypeptides
produced in cell-free expression systems (1-10 nM).
Consequently, even minimal nonspecific contamination of the ribosomal
fraction by these large particles would be sufficient to accommodate a
substantial proportion of the nascent polypeptides upon release from
the ribosomes. Careful examination of polyribosomes from E. coli (38) as well as those carrying nascent rhodanese chains
in vitro (14) revealed no GroEL interaction with the nascent
polypeptides. On the contrary, only after release from ribosomes have
polypeptides been found in transient association with GroEL. In studies
of eucaryotic mitochondrial proteins, their interactions with members
of the HSP 60 family have been observed following completion of
synthesis and/or translocation of the polypeptides (45). The suggestion
that GroEL and TRiC, unlike other HSP 60 chaperones, are involved in
interactions with nascent chains, requires further substantiation.
Protein disulfide isomerase
(PDI)1 has been shown to
affect folding of disulfide-containing proteins, both in
vivo and in vitro. PDI can be cross-linked to nascent
polypeptides in vivo (48, 49). Moreover, it has been
demonstrated that PDI is essential for efficient cotranslational
formation of disulfide bonds in a coupled translation/translocation
system (50). Eucaryotic peptidylprolyl isomerase (PPI) residing in the
endoplasmic reticulum forms transient complexes with translocating
polypeptides (49). E. coli trigger factor, found in
association with nascent polypeptides, possesses PPI activity (51, 52),
but there is no evidence yet regarding catalysis of prolyl bond
isomerization of nascent polypeptides.
Renaturation of some proteins is improved by
the presence of ribosomes (53, 54). The effect of ribosomes on protein
refolding has been attributed to the large ribosomal subunit, specifically to its RNA, the 23 S and 28 S RNA of procaryotic and
eucaryotic ribosomes, respectively (53, 54). Domain V, which is
involved in the peptidyltransferase center on the large ribosomal
subunit, has been implicated in the effect of the RNA on protein
renaturation. These observations raise the question whether ribosomes
can play an active role in biosynthetic protein folding.
subunit is rate-limiting in the
formation of the native heterodimer when prefolded subunit
is available at a sufficiently high concentration (55). Coexpression of
both subunits leads to much slower formation of the native enzyme, apparently because association becomes the rate-limiting step (56).
with determines the
overall rate of enzyme formation. The subunit released from the
ribosome associates with the subunit much faster than does
i, which predominates in refolding experiments, suggesting that the structure of the subunit when it is released from the ribosome is different from i. Whereas in
refolding experiments all molecules begin to refold at the same time
upon dilution into native conditions, in the expression system, there
is a steady-state rate of appearance of newly synthesized polypeptides,
which necessitates careful analysis of the data (6, 55). It was
concluded that the subunit produced by biosynthetic folding is a
folding intermediate which is beyond a rate-limiting step encountered
during refolding of the subunit (55).
-spectrin SH3 domain
revealed that the folding of these permuted sequences is significantly
slower and the yield is lower than that of the wild-type (59, 60). For
proteins with the N and C termini distantly positioned on the surface,
only slight rearrangements of N- and C-terminal secondary structural
elements without disruption of the folded core of the protein results
in bringing the termini into close proximity, suggesting that the final
step in folding may involve binding of the termini to the surface of
the folded core (61).
To whom correspondence should be addressed. Tel.: 409-845-1782;
Fax: 409-845-4946: E-mail: baldwin{at}bioch.tamu.edu.
1
The abbreviations used are: PDI, protein
disulfide isomerase; PPI, peptidylprolyl isomerase.
2
Yu. Alakhov, Institute of Bioorganic
Chemistry, Pushino, Russia, personal communication.
Volume 272, Number 52,
Issue of December 26, 1997
pp. 32715-32718
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
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C. Huang, G. Morales, A. Vagi, K. Chanasyk, M. Ferrazzi, C. Burklow, W.-T. Qiu, E. Feyfant, A. Sali, and R. L. Stevens Formation of Enzymatically Active, Homotypic, and Heterotypic Tetramers of Mouse Mast Cell Tryptases. DEPENDENCE ON A CONSERVED Trp-RICH DOMAIN ON THE SURFACE J. Biol. Chem., January 7, 2000; 275(1): 351 - 358. [Abstract] [Full Text] [PDF]
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M. Bogdanov and W. Dowhan Lipid-assisted Protein Folding J. Biol. Chem., December 24, 1999; 274(52): 36827 - 36830. [Full Text] [PDF]
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G. C. Meacham, B. L. Browne, W. Zhang, R. Kellermayer, D. M. Bedwell, and D. M. Cyr Mutations in the Yeast Hsp40 Chaperone Protein Ydj1 Cause Defects in Axl1 Biogenesis and Pro-a-factor Processing J. Biol. Chem., November 26, 1999; 274(48): 34396 - 34402. [Abstract] [Full Text] [PDF]
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S. Pal, S. Chandra, S. Chowdhury, D. Sarkar, A. N. Ghosh, and C. D. Gupta Complementary Role of Two Fragments of Domain V of 23 S Ribosomal RNA in Protein Folding J. Biol. Chem., November 12, 1999; 274(46): 32771 - 32777. [Abstract] [Full Text] [PDF]
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Y. Shimada, M. Nakamura, Y. Naito, K. Nomura, and Y. Ohno-Iwashita C-terminal Amino Acid Residues Are Required for the Folding and Cholesterol Binding Property of Perfringolysin O, a Pore-forming Cytolysin J. Biol. Chem., June 25, 1999; 274(26): 18536 - 18542. [Abstract] [Full Text] [PDF]
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L. Pelkmans and A. Helenius Expression of Antibody Interferes with Disulfide Bond Formation and Intracellular Transport of Antigen in the Secretory Pathway J. Biol. Chem., May 14, 1999; 274(20): 14495 - 14499. [Abstract] [Full Text] [PDF]
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J. R. Mattingly Jr., C. Torella, A. Iriarte, and M. Martinez-Carrion Conformation of Aspartate Aminotransferase Isozymes Folding under Different Conditions Probed by Limited Proteolysis J. Biol. Chem., September 4, 1998; 273(36): 23191 - 23202. [Abstract] [Full Text] [PDF]
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K. Adachi, Y. Zhao, T. Yamaguchi, and S. Surrey Assembly of gamma - with alpha -Globin Chains to Form Human Fetal Hemoglobin in Vitro and in Vivo J. Biol. Chem., April 21, 2000; 275(17): 12424 - 12429. [Abstract] [Full Text] [PDF]
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M. Widmann and P. Christen Comparison of Folding Rates of Homologous Prokaryotic and Eukaryotic Proteins J. Biol. Chem., June 16, 2000; 275(25): 18619 - 18622. [Abstract] [Full Text] [PDF]
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M. Chevalier, H. Rhee, E. C. Elguindi, and S. Y. Blond Interaction of Murine BiP/GRP78 with the DnaJ Homologue MTJ1 J. Biol. Chem., June 23, 2000; 275(26): 19620 - 19627. [Abstract] [Full Text] [PDF]
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L.-Y. Chen, B. Lin, C.-J. Pan, H. Hiraiwa, and J. Y. Chou Structural Requirements for the Stability and Microsomal Transport Activity of the Human Glucose 6-Phosphate Transporter J. Biol. Chem., October 27, 2000; 275(44): 34280 - 34286. [Abstract] [Full Text] [PDF]
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