| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 39, 30372-30377, September 29, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the
Received for publication, June 6, 2000, and in revised form, July 12, 2000
The microsomal triglyceride transfer protein
(MTP) and apolipoprotein B (apoB) belong to the vitellogenin (VTG)
family of lipid transfer proteins. MTP is essential for the
intracellular assembly and secretion of apoB-containing lipoproteins,
the key intravascular lipid transport proteins in vertebrates. We
report the predicted three-dimensional structure of the C-terminal
lipid binding cavity of MTP, modeled on the crystal structure of the lamprey VTG gene product, lipovitellin. The cavity in MTP resembles those found in the intracellular lipid-binding proteins and
bactericidal/permeability-increasing protein. Two conserved helices,
designated A and B, at the entrance to the MTP cavity mediate lipid
acquisition and binding. Helix A (amino acids 725-736) interacts with
membranes in a manner similar to viral fusion peptides. Mutation of
helix A blocks the interaction of MTP with phospholipid vesicles
containing triglyceride and impairs triglyceride binding. Mutations of
helix B (amino acids 781-786) and of N780Y, which causes
abetalipoproteinemia, have no impact on the interaction of MTP with
phospholipid vesicles but impair triglyceride binding. We propose that
insertion of helix A into lipid membranes is necessary for the
acquisition of neutral lipids and that helix B is required for their
transfer to the lipid binding cavity of MTP.
Chylomicrons (CM)1 and
very low density lipoproteins (VLDL) are among the largest
macromolecular complexes secreted from eukaryotic cells. The assembly
of neutral lipids and phospholipids into CM and VLDL is nucleated
around a single molecule of apoB and requires a microsomal triglyceride
transfer protein (MTP) complexed to the endoplasmic
reticulum-resident protein, protein disulfide isomerase (PDI).
The function of the MTP-PDI complex is to supply apoB with sufficient
lipid to form a soluble lipoprotein. Defects of apoB and MTP cause
hypobetalipoproteinemia and abetalipoproteinemia, respectively (1,
2).
ApoB and MTP have structural homology with lamprey lipovitellin (LV)
(3). LV contains an N-terminal Here, we have addressed the mechanism by which MTP-PDI acquires neutral
lipid from phospholipid bilayers for the assembly of VLDL and CMs. In
the absence of a crystal structure for MTP, we derived a homology model
to guide mutagenesis and biophysical studies. The experimental data
substantiate the overall predictions of the model and provide insights
into the mechanism of lipid acquisition and binding.
Modeling--
Models were developed on the alignment shown in
Fig. 1 and the x-ray crystal structure of lamprey LV (Protein Data
Bank accession number 1LLV), refined to an R-value of
0.19 at 2.8 Å resolution (4). The C-sheet was modeled using INSIGHT
interactive graphics software and the Homology computer program (Biosym
Technologies, San Diego) and the A-sheet with the general purpose
modeling program O (9). Models were energy minimized and the quality of
the coordinates assessed as described (3).
Mutagenesis and Expression Studies--
Mutagenesis was
performed by a polymerase chain reaction-based strategy (3). All
constructs were sequenced before use. Transfections, preparation of
cell extracts, and triglyceride transfer activities were performed as
described (2, 3).
Triglyceride Binding and Fusogenic Activity--
Wild-type (WT)
and mutant MTP-PDI complexes were purified as described (10). Donor
small unilamellar vesicles (SUVs) were prepared as described
(2), purified to homogeneity (11), and incubated with MTP
(w/w 70:1) for 2 h at 37 °C. Lipid-protein complexes were
separated on a Sepharose CL-4B (26/100) column.
Peptide Assays and Conformational Studies--
Peptides were
synthesized and purified as described (11) and dissolved (1 mg/ml) in
trifluoroethanol. Calcein leakage from SUVs was monitored as described
(12). Lipid mixing between labeled and unlabeled vesicles was measured
by a fluorescence probe dilution assay (12). The predicted
conformation of MTP peptide A at the water-lipid interface was
determined as described (13).
To build a model of the lipid binding cavity of MTP, we examined
the crystal structure of lamprey LV (Fig.
1) and an alignment of the MTPs and VTGs
(3) (Fig. 2). The walls of the lipid binding cavity of LV comprise two
The alignment of the predicted C-sheet of human MTP (amino acids
613-722) with amino acids 624-768 of lamprey LV is an extension of
the multiple sequence alignment of Mann et al. (3). (Fig. 2). At the gene level, amino acids
613-684 of MTP and the homologous residues of the VTGs are encoded by
conserved exons (5). The gaps between amino acids 681-682 and 688-689
of MTP span amino acids 694-702 and 710-734 of lamprey LV.
These regions are either proteolytically removed from the LV
homodimer or form part of the connecting structures (4). Thus, the
alignment is consistent with the evolutionary preference for
insertions/deletions to occur in regions connecting the secondary
structure (14). The alignment also reveals homology between the first
126 amino acids of the A-sheet of lamprey LV and residues 723-825 of
MTP. The alignment between amino acids 747-807 of MTP and residues
800-875 of lamprey LV was manually adjusted on the basis of the
secondary structure of lamprey LV and the amphipathic sequences of MTP.
In the alignment, a high proportion of the hydrophobic residues in this
region of MTP are superimposed onto amino acids in lamprey LV that
point inward toward the lipid binding cavity (Fig. 2). Hydrophobic
amino acids are known to be favored within internal sequences of
secondary structures and disfavored within loops or connecting
structures (15).
A Mechanism of Membrane Neutral Lipid Acquisition by the
Microsomal Triglyceride Transfer Protein*
,,,
, and**
Molecular Medicine Group, MRC Clinical
Sciences Centre, and National Heart and Lung Institute, Imperial
College School of Medicine, Hammersmith Hospital, Du Cane Road, London
W12 ONN, United Kingdom, the § Department of Biochemistry,
University of Minnesota Medical School, Minneapolis, Minnesota
55455-0326, and the ¶ Department of Biochemistry, Laboratorium
voor Lipoproteine Chemie, University of Gent, Hospitaalstraat 13, 8-9000 Gent, Belgium
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS AND DISCUSSION
REFERENCES
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS AND DISCUSSION
REFERENCES
-barrel (amino acids 17-296), an
-helical structure (amino acids 297-614), and a C-terminal lipid binding cavity (4). The structural relationship between MTP,
apoB, and LV is supported by conservation of the gene and protein
structure (3, 5). Important features of the quaternary structure of the
lamprey LV homodimer are adapted in MTP to form a heterodimer with PDI
and to associate with apoB during lipoprotein production (3, 5). The
defining difference between MTP, apoB, and LV is related to their
C-terminal lipid binding structures, which associate with different
amounts of lipid (3). LV binds principally phospholipid with a
stoichiometry of ~35 molecules/subunit (6). MTP binds 1-5 molecules
of lipid (7). ApoB has a long C-terminal extension (~3500 amino
acids), which incorporates a large neutral lipid core (8).
EXPERIMENTAL PROCEDURES
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS AND DISCUSSION
REFERENCES
RESULTS AND DISCUSSION
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS AND DISCUSSION
REFERENCES
-sheets, designated C and A, and a small section of the -helical
domain. The C-sheet comprises seven strands and the A-sheet, 23 (4).
View larger version (53K):
[in a new window]
Fig. 1.
Ribbon diagram of the LV
monomer, viewed in stereo through the funnel-shaped cavity.
The N-terminal -barrel is shown in green, the
helical domain in yellow, and the C-sheet domain in
red. -Strands 2-5 and helices A and B of the A-sheet are
shown in dark blue. Strands 6-23 are in cyan.
Two lipid ligands are drawn in orange.
View larger version (72K):
[in a new window]
Fig. 2.
Sequence alignment of the C- and A-sheet
domains of the lamprey LV precursor, VTG, with representative VTGs and
MTPs. Amino acids depicted in cyan have similar values
(>0.5) (31) in five or more sequences or in three MTPs and lamprey LV.
Residues highlighted in yellow point toward the
lipid binding cavity of lamprey LV or the predicted lipid binding
cavity of human (H.s) MTP. Underlined
residues (664 in Homo sapiens (H.s)
MTP, 681 and 683 in Xenopus laevis (X.l) and
chicken (G.g, Gallus gallus) VTG, respectively) show
conserved intron/exon boundaries, the codon sequence of which is
interrupted at the same position. Arrows indicate
-strands. Cylinders depict -helices. Loops
are shown in gray and residues with unassigned coordinates
by a dashed line. The first strands of the C
(red)- and A (blue)-sheets of lamprey LV, formed
by amino acids 196-197 and 188-190, respectively, are not predicted
for MTP (3). B.t, Bos taurus; M.a,
Mesocricetus auratus (golden hamster); C.e,
Caenorhabditis elegans; F.h, Fundulus
heteroclitus (kilifish); I.u, Ichthyomyzon
unicuspus (lamprey). Accession numbers are documented
elsewhere (3).
The alignment suggests conservation of the lipid binding C-sheet of
lamprey LV and of the lipid binding portions of -strands 2-5 of the
A-sheet of lamprey LV in MTP. Common helical motifs in the MTP sequence
also support the conservation of helix A and B of lamprey LV in MTP.
Helix A contains an N-terminal sequence (PISVV) conforming to a
proline-box motif (16). This motif includes an N-cap proline
residue, has a preference for a valine residue at the third position
(Val727) of the helix, and apolar residues at the
1 and fourth positions. Helix B contains asparagine
(Asn780) as the N-cap residue, the most common
residue at such a position (17).
The Lipid Binding Cavity of MTP--
We used the realigned
sequence of amino acids 613-826 of MTP and the atomic coordinates of
lamprey LV to derive the model of the lipid binding structures of MTP.
These structures in MTP may also include amino acids 827-894, but
extensive sequence divergence from the LVs in this region precludes an
evaluation. The models of the C- and A-sheets of MTP predict a
hydrophobic cavity, consistent with biochemical studies (18). The MTP
cavity is similar to, albeit smaller than, that found in lamprey LV
(Fig. 3, a and
b). Important evidence for the validity of the MTP structure
derives from the finding that the predicted lipid binding surfaces
contain a number of hydrophobic residues comparable to that found on
the equivalent surface of lamprey LV (Fig. 3, a and
b).
|
The predicted C-sheet domain (amino acids 603-712) of the lipid
binding cavity of MTP contains six anti-parallel -strands, and a
short helix (Fig. 3b). The model of the A-sheet domain of MTP (amino acids 725-829) comprises four -strands and two
-helices, designated A (residues 725-736) and B (residues 781-786)
(Fig. 3, a-c). Analogous to LV (Fig. 1),
these helices reside in close proximity at the entrance to the
lipid binding cavity of MTP (Fig. 3d). We envisage the back
of the cavity of MTP closed off by dimerization with PDI, since the
posterior openings to the lipid binding cavities of lamprey LV are
closed off by homodimerization (4).
The predominantly -sheet structure predicted for the lipid binding
cavity of MTP is reminiscent of the lipid binding cavities of
bactericidal/permeability-increasing protein (BPI) (19) and the fatty
acid-binding proteins (FABPs) (20, 21). The BPI family of proteins
includes phospholipid transfer protein and cholesteryl ester transfer
protein (CETP) (19). The FABPs have a common topology comprising 10 antiparallel -strands arranged in two -sheets, typically having
two short -helices that loop out to cover the mouth of the cavity.
The helices are not required for the structural integrity of the lipid
binding cavity (21). Rather, they regulate the kinetics of ligand
transfer (21).
The Entrance to the Cavity--
The functional importance of
helices A (amino acids 725-736) and B (amino acids 781-786), located
at the entrance of the lipid binding cavity of MTP, is suggested by the
abetalipoproteinemia N780Y mutation (22). Expression of MTP N780Y in
COS-1 cells produced near WT levels of soluble MTP (Fig.
4a) but no triglyceride transfer activity (Table I). The control
mutant, N780A, produced near WT activity. Our model of MTP predicts
that Asn780 forms the N-cap residue of helix B,
and because a tyrosine is rarely found at this position (17), it is
conceivable that the N780Y mutation prevents the formation of helix B. Alternatively, the tyrosine residue may, as predicted by our model
(data not shown), perturb the alignment of helix B with helix A. The
changes in the N780A model are modest, the most significant being the loss of a hydrogen bond between Asn780 and the main chain
carbonyl oxygen atom of Val778.
|
|
To further evaluate the importance of helices A and B of MTP for the lipid transfer process, we introduced mutations predicted to destabilize their packing (Fig. 3c). The individual substitution of Ile732, Tyr771, Arg772, and Lys775 with alanine had a marked impact on lipid transfer activity (Table I), despite recovery of WT or near WT levels of soluble MTP (Fig. 4a). In the MTP model, the side chain atoms of these residues form an extensive network of interactions stabilizing the spatial arrangement between helices A and B. By contrast, alanine substitution of Ile725, Val728, Leu733, Ile735, Arg777, and Ile790, which are predicted to form few or no interactions, had no impact (Fig. 3c).
Helices A and B are located at the entrance to the lipid binding cavity of MTP. There, they form a hydrophobic ridge at the water-lipid interface (Fig. 3d), which we envisage as interacting with a lipid membrane during the lipid transfer process. The importance of amino acids (Val727, Leu731, Leu734, Arg781, Val782, Val785, and Ile786) at the water-lipid interface was examined by alanine-scanning mutagenesis. Mutant proteins were individually expressed in COS-1 cells and WT levels of soluble MTP recovered (Fig. 4a). Triglyceride transfer activity was reduced in cells expressing L734A, R781A, and V782A, the activities being 33 ± 8, 59 ± 3, and 26 ± 4% of WT, respectively (Table I). The importance of Leu734 and Val782 for triglyceride transfer activity was confirmed by the markedly reduced activity of the double mutant L734A/V782A (Fig. 4a, Table I). In contrast, the individual combination of L731A, V785A, or I786A with L734A had no additional effect (Table I).
To further evaluate the functional importance of size, hydrophobicity, and geometry of residues at positions 734 and 782 of MTP, we mutated Val782 to Leu and Leu734 to Ser, Val, Ile, Phe, and Met (Fig. 4a). The activities of L734M, V782L, L734I, L734V, L734F, and L734S were 132 ± 28, 120 ± 9, 102 ± 13, 78 ± 17, 47 ± 9, and 31 ± 6 of WT, respectively (Table I). Thus, with the exception of L734F, there appears to be good agreement between MTP-mediated triglyceride transfer activity and the ranking order of the mutants with respect to size and hydrophobicity of residues at positions 734 and 782. The impaired activity of L734F may result from destabilization of helix A. Our model predicts that a phenylalanine residue at position 734 would cause steric hindrance with Gln739.
Lipid Binding and Fusogenic Properties of MTP-- WT and mutant MTP-PDI complexes were individually incubated with phospholipid vesicles containing radiolabeled triglyceride and evaluated for the dual MTP function of lipid interaction and triglyceride binding (Fig. 4, b and c). From 13C NMR spectroscopic studies (23) we envisage that the carbonyl groups of vesicle-solubilized triglyceride reside close to the vesicle surface. WT MTP-PDI increased the size of the phospholipid vesicles (Fig. 4, b and c) and acquired radiolabeled triglyceride from vesicles (Fig. 4, b and c). The interaction of L734A with lipid was markedly impaired and the amount of radiolabeled triglyceride acquired from the vesicles reduced. V782A and N780Y acquired very little radiolabeled triglyceride despite near normal ability to interact with lipid. The interaction of the double mutant L734A/V782A with lipid was similar to L734A but no radiolabeled triglyceride was acquired (data not shown). These results, and the reduced triglyceride transfer activities of L734A, V782A, and L734A/V782A (Table I), indicate that Leu734 of helix A and Val782 of helix B facilitate the triglyceride acquisition and binding step of the MTP-mediated triglyceride transfer process. The results also suggest that helix A of MTP confers MTP with fusogenic activity. Fusion peptides were first identified in the envelope protein of viruses, where they facilitate the entry of the virus into a host cell (24). Typically, they comprise between 12 and 26 residues and are highly hydrophobic (24, 25). Predicted helix A contains 12 amino acids, 8 of which are hydrophobic. Its predicted helical structure is in accord with the helical conformation of viral fusion peptides in the active state (24, 25).
The proposition that helix A is fusogenic is also suggested by theoretical and experimental data on the isolated peptide PISVVKGLILLI. This peptide is predicted to adopt an oblique (~30° angle) orientation at a water-lipid interface (data not shown) and promote membrane destabilization. Accordingly, MTP helical peptide A causes the leakage of calcein from SUVs (Fig. 4d), intravesicular lipid mixing (Fig. 4e), and an increase in vesicle size (data not shown). Importantly, a peptide corresponding to the highly active mutant L734M increased intravesicular lipid mixing activity, suggesting a tight coupling between the lipid mixing activity of peptide A and MTP-mediated triglyceride transfer activity (Table I).
Concluding Comments--
We have used molecular modeling to derive
sufficient structural information to understand how the MTP-PDI complex
might extract neutral lipid from its sites of synthesis, in the
membranes of the endoplasmic reticulum (26) for transfer to apoB during
lipoprotein assembly. Our data indicate that MTP has a fusion peptide
at the entrance to a hydrophobic lipid binding cavity, which inserts into a lipid membrane to perturb the orientation of phospholipid acyl
chains. The formation of thermodynamically unstable inverted phases
(27) may expose the acyl chains of neutral lipid and phospholipid
monomers for interactions with helix B and the hydrophobic lipid
binding cavity of MTP. We envisage that the extraction of neutral
lipids from a membrane is further facilitated by electrostatic interactions between Arg781 of helix B and the negative
charges on the phosphate groups of bilayer phospholipid molecules. Such
interactions would be expected to increase the affinity of the cavity
entrance of MTP with lipid. The discovery of lipid-interacting helical
peptides at the entrance of the lipid binding cavities of the lipases
(28), along with the predicted cavities of CETP (29) and
lecithin cholesterol acyl transferase (30), suggests that the mechanism
of lipid acquisition described here for MTP might apply to other lipid binding proteins.
| |
ACKNOWLEDGEMENTS |
|---|
We thank Drs. G. Kemball-Cook and I. Bartok for help with the graphics work, Dr. C. Mann for reading of the manuscript, Professor L. Banaszak for important discussions and encouragement throughout this project, and Dr. A. Decout and Professors J. Vandekerckhove and R. Brasseur for help with the peptide studies.
| |
FOOTNOTES |
|---|
* This work was supported by the British Medical Research Council, the British Heart Foundation (Grants PG/97011 and PG/98032), and the Minnesota Supercomputer Institute.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
** To whom correspondence should be addressed. Tel.: 44 208 3838308; Fax: 44 208 3832028; E-mail: carol.shoulders@csc.mrc.ac.uk.
Published, JBC Papers in Press, July 12, 2000, DOI 10.1074/jbc.C000364200
| |
ABBREVIATIONS |
|---|
The abbreviations used are: CM, chylomicron; apoB, apolipoprotein B; CETP, cholesteryl ester transfer protein; FABP, fatty acid-binding protein; LV lipovitellin, MTP, microsomal triglyceride transfer protein; PDI, protein disulfide isomerase; SUVs, small unilamellar vesicles; VLDL, very low density lipoproteins; VTG, vitellogenin; WT, wild type.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS AND DISCUSSION
REFERENCES
|
|---|
| 1. | Sharp, D., Blinderman, L., Combs, K. A., Kienzle, B., Ricci, B., Wagner-Smith, K., Gil, C. M., Turck, C. W., Bourna, M. E., Rader, D. J., Aggerbeck, L. P., Gregg, R. E., Gordon, D. A., and Wetterau, J. R. (1993) Nature 365, 65-69 |
| 2. | Narcisi, T. M. E., Shoulders, C. C., Chester, S. A., Read, J., Brett, D. J., Harrison, G. B., Grantham, T. T., Fox, M. F., Povey, S., de Bruin, T. W. A., Erkelens, D. W., Muller, D P R., Lloyd, J. K., and Scott, J. (1995) Am. J. Hum. Genet. 57, 1298-13310 |
| 3. | Mann, C. J., Anderson, T. A., Read, J., Chester, S. A., Harrison, G. B., Koechl, S., Ritchie, P. J., Bradbury, P., Hussain, F. S., Amey, J., Vanloo, B., Rosseneu, M., Infante, R., Hancock, J. M., Levitt, D. G., Banaszak, L. J., Scott, J., and Shoulders, C. C. (1999) J. Mol. Biol. 285, 391-408 |
| 4. | Anderson, T. A., Levitt, D. G., and Banaszak, L. J. (1998) Structure 6, 895-909 |
| 5. | Bradbury, P., Mann, C. J., Koechl, S., Anderson, T. A., Chester, S. A., Hancock, J. M., Ritchie, P. J., Amey, J., Harrison, G., Levitt, D. G., Banaszak, L. J., Scott, J., and Shoulders, C. C. (1999) J. Biol. Chem. 274, 3149-3164 |
| 6. | Timmins, P. A., Poliks, B., and Banaszak, L. (1992) Science 257, 652-655 |
| 7. | Atzel, A., and Wetterau, J. R. (1993) Biochemistry 32, 10444-10450 |
| 8. | Segrest, J. P, Jones, M. K, Mishhra, V. K, Anantharamaiah, G. H, and Garber, D. W. (1994) Arterioscler. Thromb. 14, 1674-1685 |
| 9. | Jones, T. A., Zou, J. Y., Cowan, S. W., and Kjeldgaard, M. (1991) Acta Crystallogr. Sect. A 47, 110-119 |
| 10. | Ritchie, P. J., Decout, A., Amey, J., Mann, C. J., Read, J., Rosseneu, M., Scott, J., and Shoulders, C. C. (1999) Biochem. J. 332, 305-310 |
| 11. | Peelman, F., Goethals, M., Vanloo, B., Labeur, C., Brasseur, R., Vandekerckhove, J., and Rosseneu, M. (1997) Eur. J. Biochem. 249, 708-715 |
| 12. | Decout, A., Labeur, C., Goethals, M., Brasseur, R., and Rosseneu, M. (1998) Biochim. Biophys. Acta 1372, 102-116 |
| 13. | Voneche, V., Portetelle, D., Kettmann, R., Willems, L., Limbach, K., Paoletti, E, Ruysschaert, J. M., Burny, A., and Brasseur, R. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 3810-3814 |
| 14. | Lesk, A. M., Levitt, M., and Chothia, C. (1986) Protein Eng. 1, 77-78 |
| 15. | Callebaut, I., Labesse, G., Durand, P., Poupon, A., Canard, L., Chomilier, J., Henrissat, B., and Mornon, J. P. (1997) Cell. Mol. Life Sci. 53, 621-645 |
| 16. | Viguera, A. R., and Serrano, L. (1999) Protein Sci. 8, 1733-1742 |
| 17. | Penel, S., Hughes, E., and Doig, A. (1999) J. J. Mol. Biol. 287, 127-143 |
| 18. | Jamil, H., Dickson, J. K., Jr., Chu, G-H., Lago, M. W., Rinehart, J. K., Biller, S. A., Gregg, R. E., and Wetterau, J. R. (1995) J. Biol. Chem. 270, 6549-6554 |
| 19. | Beamer, J., Carrol, F., and Eisenberg, D. (1997) Science 276, 1861-1864 |
| 20. | Bernlohr, D. A., Simpson, M. A., Hertzel, A. V., and Banaszak, L. J. (1997) Proteins 17, 277-303 |
| 21. | Cistola, D. P., Kim, K., Rogl, H., and Frieden, C. (1996) Biochemistry 35, 7559-7565 |
| 22. | Ohashi, K., Ishibashi, S., Osuga, J. I, Harada, K, Inaba, T, Yagyu, H., and Yamada, N. (1996) Circulation 94 (suppl.), I-346 |
| 23. | Miller, K. W., and Small, D. M. (1983) Biochemistry 22, 443-451 |
| 24. | Brasseur, R, Pillot, T, Lins, L, Vandekerckhove, J., and Rosseneu, M. (1997) Trends Biochem. Sci. 22, 167-171 |
| 25. | Xing Han, Steinhauer, D. A., Wharton, S. A., and Tamm, L. K. (1999) Biochemistry 38, 15052-15059 |
| 26. | Hebbachi, A.-M., and Gibbons, G. F. (1999) Biochem. Biophys. Acta 1441, 36-50 |
| 27. | Epand, R. M. (1998) Biochem. Biophys. Acta 3, 353-368 |
| 28. | Cajal, Y., Svendsen, A., Girona, V., Patkar, S. A., and Alsina, A. (2000) Biochemistry 39, 413-423 |
| 29. | Bruce, C., Beamer, L. J., and Tall, A. R. (1998) Curr. Opin. Struct. Biol. 8, 426-434 |
| 30. | Peelman, F., Vinaimont, N., Verhe, A., Vanloo, B., Verschelde, J. L., Labeur, C., Seguret-Mace, S., Hutchinson, G., Vandekerckhove, J., Tavernier, J., and Rosseneu, M. (1998) Protein Sci. 7, 587-599 |
| 31. | Schwartz, R. M., and Dayhoff, M. O. (1979) Atlas Protein Sequences and Structure , pp. 353-358, National Biomedical Research Foundation, Washington, D. C. |
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. W. Smolenaars, O. Madsen, K. W. Rodenburg, and D. J. Van der Horst Molecular diversity and evolution of the large lipid transfer protein superfamily J. Lipid Res., March 1, 2007; 48(3): 489 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rava, G. K. Ojakian, G. S. Shelness, and M. M. Hussain Phospholipid Transfer Activity of Microsomal Triacylglycerol Transfer Protein Is Sufficient for the Assembly and Secretion of Apolipoprotein B Lipoproteins J. Biol. Chem., April 21, 2006; 281(16): 11019 - 11027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sellers, L. Hou, D. R. Schoenberg, S. R. Batistuzzo de Medeiros, W. Wahli, and G. S. Shelness Microsomal Triglyceride Transfer Protein Promotes the Secretion of Xenopus laevis Vitellogenin A1 J. Biol. Chem., April 8, 2005; 280(14): 13902 - 13905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang and D. M. Small Interfacial properties of amphipathic {beta} strand consensus peptides of apolipoprotein B at oil/water interfaces J. Lipid Res., September 1, 2004; 45(9): 1704 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sellers, L. Hou, H. Athar, M. M. Hussain, and G. S. Shelness A Drosophila Microsomal Triglyceride Transfer Protein Homolog Promotes the Assembly and Secretion of Human Apolipoprotein B: IMPLICATIONS FOR HUMAN AND INSECT LIPID TRANSPORT AND METABOLISM J. Biol. Chem., May 23, 2003; 278(22): 20367 - 20373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Hussain, J. Shi, and P. Dreizen Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly J. Lipid Res., January 1, 2003; 44(1): 22 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xie, L. A. Woollett, S. D. Turley, and J. M. Dietschy Fatty acids differentially regulate hepatic cholesteryl ester formation and incorporation into lipoproteins in the liver of the mouse J. Lipid Res., September 1, 2002; 43(9): 1508 - 1519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Chang, C. C. Y. Chang, X. Lu, and S. Lin Catalysis of ACAT may be completed within the plane of the membrane: a working hypothesis J. Lipid Res., December 1, 2001; 42(12): 1933 - 1938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bakillah and M. M. Hussain Binding of Microsomal Triglyceride Transfer Protein to Lipids Results in Increased Affinity for Apolipoprotein B. EVIDENCE FOR STABLE MICROSOMAL MTP-LIPID COMPLEXES J. Biol. Chem., August 10, 2001; 276(33): 31466 - 31473. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
