| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 33, 25057-25060, August 18, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
§ and
From the Department of Chemistry and Department of
Biochemistry, Molecular Biology and Cellular Biology, Northwestern
University, Evanston, Illinois 60208-3113 and the
¶ Department of Environmental Health Sciences, The Johns
Hopkins University School of Public Health,
Baltimore, Maryland 21205
Enzymes that employ transition metals as
co-factors are housed in a wide variety of intracellular locations or
are exported to the extracellular milieu. A key question then arises:
how are specific metal co-factors transported to diverse locations and subsequently sorted into the correct metalloenzymes? The mechanisms by
which these tasks are accomplished are just now being unraveled. A new
family of soluble metal receptor proteins known as
"metallochaperones" is emerging that act in the intracellular
trafficking of metal ions. Although transition elements can be quite
toxic, these metal receptors are not detoxification proteins; they
clearly function in a "chaperone-like" manner, guiding and
protecting the metal ion while facilitating appropriate partnerships.
Here we will review the most recent advances in our understanding of
copper metallochaperones and discuss mechanisms that may be relevant to
other essential, yet potentially toxic, metal ions.
The concept of copper metallochaperones is relatively new; prior
to 1997, there were no established molecules that served this function.
In vitro, most copper enzymes easily acquire their metal
without an auxiliary protein. For example, the copper- and zinc-dependent enzyme superoxide dismutase
(SOD1)1 binds copper ions
in vitro with an extraordinarily high affinity (Kd Employing the yeast cell as a model, we have estimated the total
cytoplasmic free copper concentration to be less than
10 Cytochrome oxidase, a key mitochondrial enzyme in the respiratory
chain, requires a total of three copper ions to be inserted into two
subunits: a binuclear copper site protruding into the inner membrane
space of the mitochondria and a mononuclear site buried within
the inner membrane (3). It is not clear when or how these copper ions
are inserted into the enzyme; however, among the host of assembly
factors required for cytochrome oxidase activity, two proteins clearly
have an effect on copper utilization. One of these, COX17, is a
candidate metallochaperone.
COX17, originally discovered by Tzagoloff and co-workers (4,
5), is an 8.0-kDa protein bearing 6 cysteines that are conserved in the
yeast and human proteins. Yeast COX17 localizes to both the cytosol and
inner membrane space of the mitochondria, consistent with a role as a
shuttle protein for delivering copper to mitochondria (6). Winge
and co-workers (7) have shown that a copper-loaded COX17 can be
isolated from Escherichia coli expression systems with Cu(I)
ions bound in a sulfide and cysteine thiolate cluster. It is noteworthy
that COX17 is predicted to require only four of the six conserved
cysteinyl residues for metal coordination (7).
Copper incorporation into yeast cytochrome oxidase also requires the
presence of SCO1, a mitochondrial inner membrane protein (8). SCO2, a
homologue of SCO1, may also play a role in activation of cytochrome
oxidase (9). SCO1 shares homology with subunit 2 of cytochrome oxidase,
including two conserved copper-binding cysteinyl ligands (6, 9). It is
possible that this region directly transfers copper to cytochrome
oxidase, whereas COX17 may act as the shuttle protein to deliver copper
to mitochondrial factors such as SCO1/SCO2. Until specific partnerships
are established by biochemical or genetic means, alternative models
cannot be excluded.
We originally identified ATX1
(anti-oxidant) in 1995 as a gene
that afforded protection against oxidative damage in yeast (10). This
anti-oxidant protection requires ATX1 overproduction but may not be
physiologically relevant because activity appears to result from
stoichiometric, not catalytic, consumption of superoxide by Cu-ATX1
(11). Subsequently, ATX1 was found to specifically shuttle copper to an
intracellular copper transporter located in the Golgi compartment of
the secretory pathway (12-14). This copper transporter then pumps the
metal into the lumen of the Golgi for insertion into copper enzymes
destined for the cell surface or extracellular environment. Following
identification of yeast ATX1, the human homologue was isolated by
Gitlin and colleagues (15, 16) and has been denoted HAH1 or ATOX1.
The targets of copper delivery by ATX1 are P-type copper transporters
that are also conserved among eukaryotes. These transporters are
members of a large family of transporting ATPases that use energy from
ATP hydrolysis to drive membrane transport of ions (reviewed in Ref.
17). Humans express two forms of this transporter, known as ATP7A and
ATP7B. Inherited mutations in these copper transporters are responsible
for Menkes syndrome and Wilson's disease, specific human disorders of
copper metabolism (reviewed in Ref. 18). Yeast express a similar copper
transporter known as CCC2 that is needed for activating the FET3 copper
protein involved in iron uptake (19) (Fig.
1). A plant version of the copper
transporter has been identified as RAN1 and functions together with an
ATX1-like molecule to modulate plant growth in response to ethylene
(20, 21).
INTRODUCTION
The Requirement for Copper Metallochaperones
10
15
M). Yet in a living cell, where total copper
concentrations are in the micromolar range, SOD1 relies heavily upon an
auxiliary factor for acquiring copper. This paradox is resolved by
recent observations that establish an upper limit on the number of
"free" copper ions available in the cytoplasm of an unstressed cell
(1, 2).
18 M, which represents many
orders of magnitude less than one atom of free copper per cell (1). In
this usage, "free" copper is a thermodynamic term, which
corresponds to aquo (hydrated) Cu(I) or Cu(II) complexes not
coordinated by tight binding ligands such as amino acids or
biopolymers. A similar conclusion regarding the scarcity of free
intracellular copper ions can also be derived in kinetic terms; less
than 0.01% of the total cellular copper becomes free in the cytoplasm
during the lifetime of the cell (1). This apparent absence of free
copper can be attributed to a wide variety of moderate and tight
binding chelation sites in the cell including nonspecific small
molecule interactions, as well as vesicular sites for concentration of
the metal and specific copper proteins. This copper chelation capacity
becomes even more potent when copper detoxification systems such as
metallothioneins are induced. Despite this backdrop of cellular
overcapacity for copper chelation, metallochaperones succeed in
acquiring the metal and donating it to enzymes that need it (depicted
in Fig. 1). Thus far, three distinct copper trafficking pathways have
been described for copper, and these will be discussed independently.
Delivery of Copper to the Mitochondria
The ATX1 Pathway of Copper Delivery to the Golgi
View larger version (80K):
[in a new window]
Fig. 1.
Copper trafficking pathways in
eukaryotes. Known pathways for the delivery of copper in
yeast are depicted. Copper uptake, mediated in part by the cell surface
copper transporter (Ctr) (47), is eventually deployed
to mitochondrial cytochrome oxidase
((Cytox) via a pathway involving Cox17 and
Sco), to cytosolic SOD1 (via a pathway involving CCS), or to the
copper transporter CCC2 and the multicopper oxidase Fet3 in the
secretory pathway (involving ATX1). Cytosolic concentrations of free
copper are typically maintained at exquisitely low levels
(<10 18 M) by metal scavenging
systems including metallothioneins (MT) (1).
Dashed arrows represent undefined pathways
whereas solid arrows indicate established copper
transfer steps discussed in the text.
The yeast ATX1 copper chaperone is known to bind a single metal ion via
two cysteine residues present in the ATX1 amino acid sequence
MXCXXC (where M is methionine, X is
any amino acid, and C is cysteine) (13). The metal-binding site in ATX1
is flexible and accommodates additional bonding interactions with the
Cu(I) atom, indicating that the protein readily allows changes in
coordination number of the bound metal. This type of coordination
environment was unprecedented in copper proteins but is now emerging as
a common feature of copper trafficking proteins. Structural studies of
ATX1, the copper chaperone for SOD1 (CCS), bacterial CopZ, and the
metal-binding domains of the copper transporters that serve as targets
for ATX1 have been reviewed elsewhere (22). In all cases, the
polypeptides adopt a 
fold with a similar tertiary
structure in which two -helices are superimposed on a 4-stranded
-sheet with a solvent-exposed metal-binding site. In ATX1,
this fold has been shown to provide a tight Cu(I)-binding site and protects the metal center from both oxidants and from capture
by excess competing thiols such as glutathione (13).
How does the Cu-ATX1 complex specifically recognize, dock with, and
then transfer copper to the P-type metal transporter? ATX1 has been
shown to physically interact with the ATX1-like domains of the copper
transporter through a process involving copper ions and the
MXCXXC copper site (11, 13, 23, 24). Docking of
ATX1 also appears to involve electrostatic interactions between a
positively charged face of ATX1 and negatively charged residues on the
analogous segment of the copper transporter (11, 25) (Fig.
2). Once the metallochaperone has docked
with its target, a cysteine from the acceptor domain is proposed to
attack the Cu(I) center in ATX1. This initiates the formation and decay of a series of two- and three-coordinate Cu(I) centers in which the
coordinated cysteines of ATX1 are sequentially replaced with cysteines
of the copper transporter domains (13) (Fig. 2).
|
The thermodynamic gradient for metal exchange between ATX1 and CCC2 has
been shown to be quite shallow, with a Cu(I) exchange equilibrium
constant of 1.4 (26). Although this result reveals that ATX1 can
release Cu(I) from a tight binding site, it begs the question of how
the metallochaperone can provide sufficient flux of copper to the
transporters. The present data suggest that ATX1 functions like an
enzyme; it lowers the activation barrier for Cu(I) transfer with
partner proteins and perhaps discriminates against non-partners as
well. In support of this notion, copper is observed to rapidly
equilibrate between ATX1 and CCC2, and the equilibrium is insensitive
to an excess of copper scavengers that are common to the intracellular
milieu. The ultimate driving force for copper transfer is then provided
by other domains of the transporter, which employ ATP hydrolysis to
remove Cu(I) to a separate thermodynamic compartment where multicopper
oxidases and other apoproteins obtain the metal (26).
| |
Copper Delivery to Cytosolic Superoxide Dismutase |
|---|
The target for CCS is a soluble copper- and zinc-requiring enzyme SOD1 (27). SOD1 protects cells against oxidative damage by scavenging toxic superoxide anion radicals through redox reactions at the bound copper ion. The in vivo insertion of copper into SOD1 requires a copper metallochaperone that was first identified in yeast as a gene involved in the lysine biosynthetic pathway, namely LYS7 (28-30). Yeast mutants lacking LYS7 express a form of SOD1 that is essentially apo for copper (29, 31) but contains a single atom of zinc per dimer SOD1 (31). The identification of the yeast metallochaperone for SOD1 quickly led to the cloning of the human homologue that had previously been identified as SOD4, a putative SOD isoform (29). Both yeast and human proteins have been denoted as CCS. Mice with targeted disruptions in CCS exhibit marked reductions in SOD1 activity, emphasizing the conserved requirement for CCS in activation of eukaryotic SOD1 (32).
CCS is the largest of copper metallochaperones identified to date.
Whereas ATX1 and COX17 represent single domain proteins, CCS folds into
three functionally distinct protein domains (Figs. 1 and
3) (33-36). The N-terminal Domain I of
CCS bears striking homology to ATX1, including the
MXCXXC copper-binding site. Surprisingly, however, a CCS molecule lacking this domain can still insert copper into SOD1 in vivo, provided the cell is not starved for
copper (33). We therefore proposed that this ATX1-like domain is only needed to maximize CCS function under extreme copper-limiting conditions.
|
The central domain of CCS (Domain II) is homologous to its target of copper delivery, SOD1 (31, 34-38). With human CCS, this homology is so strong that a single mutation in Domain II is sufficient to turn CCS into a SOD-like molecule with superoxide scavenging activity (38). Domain II physically interacts with SOD1 (37) and is proposed to secure the enzyme during copper insertion. SOD1 normally exists as a homodimer, and formation of a transient heterodimer or a heterotetramer between SOD1 and CCS may precede copper transfer (34-36, 38) (Fig. 3).
The C-terminal Domain III of CCS is quite small (30 amino acids) yet
is extremely crucial for activating SOD1 in vivo (33). This
peptide is highly conserved among CCS molecules from diverse species
and includes an invariant CXC motif that can bind copper (33). Domain III was disordered in the crystal structure; however, this
domain is predicted to lie in the vicinity of the N-terminal Domain I
(36, 39). Models have been proposed in which Domain III, perhaps in
concert with the N-terminal copper site, directly inserts copper into
the active site of SOD1 (33, 40). The mechanism of copper movement from
an all-sulfur coordination environment (in CCS) to the all-nitrogen
site in SOD1 remains an open issue.
It is noteworthy that human CCS may have some important relevance
regarding the fatal motor neuron disease, familial amyotrophic lateral
sclerosis (FALS). A subset of FALS cases results from dominantly
inherited mutations in SOD1, and toxicity from the bound copper ion has
been the designated culprit in certain models (41). Because FALS SOD1
mutants rely on the CCS (42) and mammalian CCS is abundantly expressed
in neuronal tissue (43), CCS may play some part in the etiology of
FALS.
| |
Metallochaperones in Prokaryotes |
|---|
Prokaryotes lack the intracellular compartmentalization that is
typical of eukaryotes; thus organelle-specific carriers of metals such
as COX17 may not be essential. Furthermore, bacteria express a copper
and zinc SOD, but no prokaryotic homologue to CCS has been identified.
However, a homologue to ATX1 (CopZ) has been described for enteric
bacteria. CopZ was originally proposed to function as a copper
transcription factor; yet based on its sequence and structural homology
to ATX1, CopZ is a likely copper metallochaperone. Purified CopZ has
the capacity to donate copper to the CopY transcription factor in
vitro, and a model has been proposed in which this transfer of
copper displaces the zinc ion needed for CopY binding to DNA (reviewed
in Ref. 44). Other targets for CopZ, such as the copper efflux pump,
have not been excluded.
| |
Metallochaperones for Metals Other than Copper? |
|---|
Although the bulk of knowledge on intracellular metal trafficking
has emanated from studies of copper-based systems, it is likely that
analogous cofactor trafficking pathways exist for other metals. Thus
far, no eukaryotic chaperones for metals other than copper have been
established; however, candidates for delivery of iron to the sites of
iron-sulfur cluster assembly have been identified, such as the IscA
family of proteins (45). Furthermore, prokaryotic nickel-binding
proteins have been described that may facilitate the insertion of the
metal into nickel-requiring enzymes, such as urease and cobalt
dehydrogenase (reviewed in Ref. 46).
| |
Conclusions |
|---|
Redox-active transition metals such as copper present a dilemma to
the cell; they are useful but dangerous cofactors. The metallochaperone
proteins clearly do not function to protect the cell from metal
toxicity. In fact, from studies in yeast, metallochaperones become
critical for cell function only under copper limitation conditions (1,
4, 12). Instead, metallochaperones ensure the safe delivery of the
metal ion to its proper intracellular destination and in the process
protect the precious cargo from adventitious reactions and a multitude
of alternative binding sites. How and where the chaperones themselves
acquire copper remain a mystery, as such factors have yet to be identified.
| |
ACKNOWLEDGEMENTS |
|---|
We thank Joan Valentine and Dennis Winge for communication of unpublished results and members of the Culotta laboratory for providing art work.
| |
FOOTNOTES |
|---|
* This minireview will be reprinted in the 2000 Minireview Compendium, which will be available in December, 2000. This review was funded by National Institutes of Health Grants GM 54111 (to T. V. O.) and GM 50016 and ES 08996 (to V. C. C.) and by support from the ALS Association (to T. V. O).
§ To whom correspondence may be addressed: 2145 Sheridan Rd., Northwestern University, Evanston, IL 60208-3113. Tel.: 847-491-5060; Fax: 847-491-7713; E-mail: t-ohalloran@nwu.edu.
To whom correspondence may be addressed: Dept. of
Environmental Health Sciences, Rm. 7032, The Johns Hopkins University
School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205-2179. Tel.: 410-955-3029; Fax: 410-955-0116; E-mail:
vculotta@jhsph.edu.
Published, JBC Papers in Press, May 16, 2000, DOI 10.1074/jbc.R000006200
| |
ABBREVIATIONS |
|---|
The abbreviations used are: SOD1, superoxide dismutase; CCS, copper chaperone for SOD1; FALS, familial amyotrophic lateral sclerosis.
| |
REFERENCES |
|---|
| 1. | Rae, T. D., Schmidt, P. J., Pufhal, R. A., Culotta, V. C., and O'Halloran, T. V. (1999) Science 284, 805-808 |
| 2. | Lippard, S. J. (1999) Science 284, 748-749 |
| 3. | Tsukihara, T., Aoyama, H., Yamashita, E., Tomizaki, T., Yamaguchi, H., Shinzawa-Itho, K., Hakashima, R., Yaono, R., and Yoshikawa, S. (1995) Science 269, 1069-1074 |
| 4. | Glerum, D. M., Shtanko, A., and Tzagoloff, A. (1996) J. Biol. Chem. 271, 14504-14509 |
| 5. | Amaravadi, R., Glerum, D. M., and Tzagoloff, A. (1997) Hum. Genet. 99, 329-333 |
| 6. | Beers, J., Glerum, D. M., and Tzagoloff, A. (1997) J. Biol. Chem. 272, 33191-33196 |
| 7. | Srinivasan, C., Posewitz, M. C., George, G. N., and Winge, D. R. (1998) Biochemistry 37, 7572-7577 |
| 8. | Schulze, M., and Rodel, G. (1989) Mol. Gen. Genet. 216, 37-43 |
| 9. | Glerum, D. M., Shtanko, A., and Tzagoloff, A. (1996) J. Biol. Chem. 271, 20531-20535 |
| 10. | Lin, S., and Culotta, V. C. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 3784-3788 |
| 11. | Portnoy, M. E., Rosenzweig, A. C., Rae, T., Huffman, D. L., O'Halloran, T. V., and Culotta, V. C. (1999) J. Biol. Chem. 274, 15041-15045 |
| 12. | Lin, S. J., Pufahl, R., Dancis, A., O'Halloran, T. V., and Culotta, V. C. (1997) J. Biol. Chem. 272, 9215-9220 |
| 13. | Pufahl, R., Singer, C., Peariso, K. L., Lin, S. J., Schmidt, P., Fahrni, C., Culotta, V. C., Penner-Hahn, J. E., and O'Halloran, T. V. (1997) Science 278, 853-856 |
| 14. | Valentine, J. S., and Gralla, E. B. (1997) Science 278, 817-818 |
| 15. | Klomp, L. W. J., Lin, S. J., Yuan, D., Klausner, R. D., Culotta, V. C., and Gitlin, J. D. (1997) J. Biol. Chem. 272, 9221-9226 |
| 16. | Hung, I. H., Casareno, R. L. B., Labesse, G., Mathews, F. S., and Gitlin, J. D. (1998) J. Biol. Chem. 273, 1749-1754 |
| 17. | Vulpe, C. D., and Packman, S. (1995) Annu. Rev. Nutr. 15, 293-322 |
| 18. | Bull, P. C., and Cox, D. W. (1994) Trends Genet. 10, 246-252 |
| 19. | Yuan, D. S., Stearman, R., Dancis, A., Dunn, T., Beeler, T., and Klausner, R. D. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 2632-2636 |
| 20. | Hirayama, T., Kieber, J. J., Hirayama, N., Kogan, M., Guzman, P., Nourizadeh, S., Alonso, J. M., Dailey, W. P., Dancis, A., and Ecker, J. R. (1999) Cell 97, 383-393 |
| 21. | Himelblau, E., Mira, H., Lin, S. J., Culotta, V. C., Penarrubia, L., and Amasino, R. M. (1998) Plant Physiol. (Bethesda) 117, 1227-1234 |
| 22. | Rosenzweig, A. C., and O'Halloran, T. V. (2000) Curr. Opin. Chem. Biol. 4, 140-147 |
| 23. | Hamza, I., Schaefer, M., Klomp, L. W. J., and Gitlin, J. D. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 13363-13368 |
| 24. | Larin, D., Mekios, C., Das, K., Ross, B., Yang, A., and Gilliam, T. C. (1999) J. Biol. Chem. 274, 28497-28504 |
| 25. | Rosenzweig, A. C., Huffman, D. L., Hou, M. Y., Wernimont, A. K., Pufahl, R. A., and O'Halloran, T. V. (1999) Structure 7, 605-607 |
| 26. | Huffman, D. L., and O'Halloran, T. V. (2000) J. Biol. Chem. 275, 18611-18614 |
| 27. | McCord, J. M., and Fridovich, I. (1969) J. Biol. Chem. 244, 6049-6055 |
| 28. | Horecka, J., Kinsey, P. T., and Sprague, G. F. (1995) Gene (Amst.) 162, 87-92 |
| 29. | Culotta, V. C., Klomp, L., Strain, J., Casareno, R., Krems, B., and Gitlin, J. D. (1997) J. Biol. Chem. 272, 23469-23472 |
| 30. | Gamonet, F., and Lauquin, G. J.-M. (1998) Eur. J. Biochem. 251, 716-723 |
| 31. | Lyons, T. J., Nerissian, A., Goto, J. J., Zhu, H., Gralla, E. B., and Valentine, J. S. (1998) J. Bioinorg. Chem. 3, 650-662 |
| 32. | Wong, P. C., Waggoner, D., Subramaniam, J. R., Tessarollo, L., Bartnikas, T. B., Culotta, V. C., Price, D. L., Rothstein, J., and Gitlin, J. D. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 2886-2891 |
| 33. | Schmidt, P., Rae, T. D., Pufahl, R. A., Hamma, T., Strain, J., O'Halloran, T. V., and Culotta, V. C. (1999) J. Biol. Chem. 274, 23719-23725 |
| 34. | Lamb, A. L., Wernimont, A. K., Pufahl, R. A., Culotta, V. C., O'Halloran, T. V., and Rosenzweig, A. C. (1999) Nat. Struct. Biol. 6, 724-729 |
| 35. | Hall, L. T., Sanchez, R. J., Holloway, S. P., Zhu, H., Stine, J. E., Lyons, T. J., Demeler, B., Schirf, V., Hansen, J. C., Nersissian, A. M., Valentine, J. S., and Hart, P. J. (2000) Biochemistry 39, 3611-3623 |
| 36. | Lamb, A. L., Wernimont, A. K., Pufahl, R. A., O'Halloran, T. V., and Rosenzweig, A. C. (2000) Biochemistry 39, 1589-1595 |
| 37. | Casareno, R. L., Waggoner, D., and Gitlin, J. D. (1998) J. Biol. Chem. 273, 23625-23628 |
| 38. | Schmidt, P. J., Ramos-Gomez, M., and Culotta, V. C. (1999) J. Biol. Chem. 274, 36952-36956 |
| 39. | Falconi, M., Iovino, M., and Desideri, A. (1999) Structure 7, 903-908 |
| 40. | Zhu, H., Shipp, E., Sanchez, R. J., Liba, A., Stine, J. E., Hart, P. J., Gralla, E. B., Nersissian, A. M., and Valentine, J. S. (2000) Biochem. J., in press |
| 41. | Cleveland, D. (1999) Neuron 24, 515-520 |
| 42. | Corson, L. B., Strain, J., Culotta, V. C., and Cleveland, D. W. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 6361-6366 |
| 43. | Rothstein, J. D., Dykes-Hoberg, M., Corson, L. B., Becker, M., Cleveland, D. W., Price, D., Culotta, V. C., and Wong, P. C. (1999) J. Neurochem. 72, 422-429 |
| 44. | Harrison, M. D., Jones, C. E., Solioz, M., and Dameron, C. T. (2000) Trends Biochem. Sci. 25, 29-32 |
| 45. | Jensen, L., and Culotta, V. C. (2000) Mol. Cell. Biol. 20, 3919-3927 |
| 46. | Hausinger, R. P. (1997) J. Bioinorg. Chem. 2, 279-286 |
| 47. | Dancis, A., Haile, D., Yuan, D. S., and Klausner, R. D. (1994) J. Biol. Chem. 269, 25660-25667 |
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Shi, K. Z. Bencze, T. L. Stemmler, and C. C. Philpott A Cytosolic Iron Chaperone That Delivers Iron to Ferritin Science, May 30, 2008; 320(5880): 1207 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Petersen, T. Kristensen, J. S. Petersen, L. Ramsgaard, T. D. Oury, J. D. Crapo, N. C. Nielsen, and J. J. Enghild The Folding of Human Active and Inactive Extracellular Superoxide Dismutases Is an Intracellular Event J. Biol. Chem., May 30, 2008; 283(22): 15031 - 15036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gonzalez-Guerrero and J. M. Arguello Mechanism of Cu+-transporting ATPases: Soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites PNAS, April 22, 2008; 105(16): 5992 - 5997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Itoh, H. W. Kim, O. Nakagawa, K. Ozumi, S. M. Lessner, H. Aoki, K. Akram, R. D. McKinney, M. Ushio-Fukai, and T. Fukai Novel Role of Antioxidant-1 (Atox1) as a Copper-dependent Transcription Factor Involved in Cell Proliferation J. Biol. Chem., April 4, 2008; 283(14): 9157 - 9167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Dick, J. W. Torpey, T. J. Beveridge, and B. M. Tebo Direct Identification of a Bacterial Manganese(II) Oxidase, the Multicopper Oxidase MnxG, from Spores of Several Different Marine Bacillus Species Appl. Envir. Microbiol., March 1, 2008; 74(5): 1527 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Chou, Y. Zhao, S. Gao, I.-N. Chou, P. Toselli, P. Stone, and W. Li Perturbation of Copper (Cu) Homeostasis and Expression of Cu-Binding Proteins in Cadmium-Resistant Lung Fibroblasts Toxicol. Sci., September 1, 2007; 99(1): 267 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Finney, S. Mandava, L. Ursos, W. Zhang, D. Rodi, S. Vogt, D. Legnini, J. Maser, F. Ikpatt, O. I. Olopade, et al. X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis PNAS, February 13, 2007; 104(7): 2247 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Banci, I. Bertini, F. Cantini, N. DellaMalva, T. Herrmann, A. Rosato, and K. Wuthrich Solution Structure and Intermolecular Interactions of the Third Metal-binding Domain of ATP7A, the Menkes Disease Protein J. Biol. Chem., September 29, 2006; 281(39): 29141 - 29147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Laliberte and S. Labbe Mechanisms of copper loading on the Schizosaccharomyces pombe copper amine oxidase 1 expressed in Saccharomyces cerevisiae. Microbiology, September 1, 2006; 152(Pt 9): 2819 - 2830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Banci, I. Bertini, S. Ciofi-Baffoni, N. G. Kandias, N. J. Robinson, G. A. Spyroulias, X.-C. Su, S. Tottey, and M. Vanarotti The delivery of copper for thylakoid import observed by NMR PNAS, May 30, 2006; 103(22): 8320 - 8325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Caruano-Yzermans, T. B. Bartnikas, and J. D. Gitlin Mechanisms of the Copper-dependent Turnover of the Copper Chaperone for Superoxide Dismutase J. Biol. Chem., May 12, 2006; 281(19): 13581 - 13587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Achila, L. Banci, I. Bertini, J. Bunce, S. Ciofi-Baffoni, and D. L. Huffman Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake PNAS, April 11, 2006; 103(15): 5729 - 5734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, C. Alexander, J. Serrano, E. Borg, and D. C. Dawson Variable Reactivity of an Engineered Cysteine at Position 338 in Cystic Fibrosis Transmembrane Conductance Regulator Reflects Different Chemical States of the Thiol J. Biol. Chem., March 24, 2006; 281(12): 8275 - 8285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Banci, I. Bertini, F. Cantini, C. T. Chasapis, N. Hadjiliadis, and A. Rosato A NMR Study of the Interaction of a Three-domain Construct of ATP7A with Copper(I) and Copper(I)-HAH1: THE INTERPLAY OF DOMAINS J. Biol. Chem., November 18, 2005; 280(46): 38259 - 38263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. van Bakel, E. Strengman, C. Wijmenga, and F. C. P. Holstege Gene expression profiling and phenotype analyses of S. cerevisiae in response to changing copper reveals six genes with new roles in copper and iron metabolism Physiol Genomics, August 11, 2005; 22(3): 356 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. C. Culotta, M. Yang, and M. D. Hall Manganese Transport and Trafficking: Lessons Learned from Saccharomyces cerevisiae Eukaryot. Cell, July 1, 2005; 4(7): 1159 - 1165. [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Alcaraz, B. Jimenez, J. M. Moratal, and A. Donaire An NMR view of the unfolding process of rusticyanin: Structural elements that maintain the architecture of a {beta}-barrel metalloprotein Protein Sci., July 1, 2005; 14(7): 1710 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Luk, M. Yang, L. T. Jensen, Y. Bourbonnais, and V. C. Culotta Manganese Activation of Superoxide Dismutase 2 in the Mitochondria of Saccharomyces cerevisiae J. Biol. Chem., June 17, 2005; 280(24): 22715 - 22720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, E. R. Lyver, S. A. B. Knight, E. Lesuisse, and A. Dancis Frataxin and Mitochondrial Carrier Proteins, Mrs3p and Mrs4p, Cooperate in Providing Iron for Heme Synthesis J. Biol. Chem., May 20, 2005; 280(20): 19794 - 19807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Angeletti, K. J. Waldron, K. B. Freeman, H. Bawagan, I. Hussain, C. C. J. Miller, K.-F. Lau, M. E. Tennant, C. Dennison, N. J. Robinson, et al. BACE1 Cytoplasmic Domain Interacts with the Copper Chaperone for Superoxide Dismutase-1 and Binds Copper J. Biol. Chem., May 6, 2005; 280(18): 17930 - 17937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Jeney, S. Itoh, M. Wendt, Q. Gradek, M. Ushio-Fukai, D. G. Harrison, and T. Fukai Role of Antioxidant-1 in Extracellular Superoxide Dismutase Function and Expression Circ. Res., April 15, 2005; 96(7): 723 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Zhang, G. Butland, J. F. Greenblatt, A. Emili, and D. B. Zamble A Role for SlyD in the Escherichia coli Hydrogenase Biosynthetic Pathway J. Biol. Chem., February 11, 2005; 280(6): 4360 - 4366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Calderone, B. Dolderer, H.-J. Hartmann, H. Echner, C. Luchinat, C. Del Bianco, S. Mangani, and U. Weser The crystal structure of yeast copper thionein: The solution of a long-lasting enigma PNAS, January 4, 2005; 102(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Arnesano, L. Banci, I. Bertini, M. Martinelli, Y. Furukawa, and T. V. O'Halloran The Unusually Stable Quaternary Structure of Human Cu,Zn-Superoxide Dismutase 1 Is Controlled by Both Metal Occupancy and Disulfide Status J. Biol. Chem., November 12, 2004; 279(46): 47998 - 48003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Won and B.-J. Lee Nickel-Binding Properties of the C-Terminal Tail Peptide of Bacillus pasteurii UreE J. Biochem., November 1, 2004; 136(5): 635 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jeong, T. A. Rouault, and R. L. Levine Identification of a Heme-sensing Domain in Iron Regulatory Protein 2 J. Biol. Chem., October 29, 2004; 279(44): 45450 - 45454. [Abstract] [Full Text] [PDF]
|
|
TOP
INTRODUCTION
The Requirement for Copper...
