A simple method for modeling transmembrane helix oligomers

被引:64
作者
Kim, S
Chamberlain, AK
Bowie, JU
机构
[1] Univ Calif Los Angeles, Dept Biochem & Chem, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, DOE Ctr Genom & Proteom, Los Angeles, CA 90095 USA
关键词
membrane protein; structure prediction; modeling; Monte Carlo optimization; glycophorin A; neu; erbB-2; M2; phospholamban;
D O I
10.1016/S0022-2836(03)00521-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We describe an effective procedure for modeling the structures of simple transmembrane helix homo-oligomers. The method differs from many previous approaches in that the only structural constraint we use to help select the correct model is the oligomerization state of the protein. The method involves the following steps: (1) perform 100-250 independent Monte Carlo energy minimizations of helix pairs to produce a large collection of well-packed structures; (2) filter the minimized structures to find those that are consistent with the expected symmetry of the oligomer; (3) cluster the structures that pass the symmetry filter; and (4) select a representative of the most populous cluster as the final prediction. We applied the method to the transmembrane helices of five proteins and compare our results to the available experimental data. Our predictions of glycophorin A, neu, the M2 channel and phospholamban resulted in a single model for each protein that agreed with the experimental results. In the case of erbB-2, however, we obtained three structurally distinct clusters of approximately equal sizes, so it was not possible to identify a clearly favored structure. This may reflect a real heterogeneity of packing modes for erbB-2, which is known to interact with different receptor subunits. Our method should be useful for obtaining structural models of transmembrane domains, improving our understanding of structure/function relationships for particular membrane proteins. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:831 / 840
页数:10
相关论文
共 54 条
[1]   Helix-helix packing and interfacial pairwise interactions of residues in membrane proteins [J].
Adamian, L ;
Liang, J .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 311 (04) :891-907
[2]   COMPUTATIONAL SEARCHING AND MUTAGENESIS SUGGEST A STRUCTURE FOR THE PENTAMERIC TRANSMEMBRANE DOMAIN OF PHOSPHOLAMBAN [J].
ADAMS, PD ;
ARKIN, IT ;
ENGELMAN, DM ;
BRUNGER, AT .
NATURE STRUCTURAL BIOLOGY, 1995, 2 (02) :154-162
[3]  
ADAMS PD, 1995, PROTEIN-STRUCT FUNCT, V26, P257
[4]   STRUCTURAL ORGANIZATION OF THE PENTAMERIC TRANSMEMBRANE ALPHA-HELICES OF PHOSPHOLAMBAN, A CARDIAC ION-CHANNEL [J].
ARKIN, IT ;
ADAMS, PD ;
MACKENZIE, KR ;
LEMMON, MA ;
BRUNGER, AT ;
ENGELMAN, DM .
EMBO JOURNAL, 1994, 13 (20) :4757-4764
[5]   ONCOGENIC ACTIVATION OF THE NEU-ENCODED RECEPTOR PROTEIN BY POINT MUTATION AND DELETION [J].
BARGMANN, CI ;
WEINBERG, RA .
EMBO JOURNAL, 1988, 7 (07) :2043-2052
[6]   The influenza virus M2 ion channel protein:: Probing the structure of the transmembrane domain in intact cells by using engineered disulfide cross-linking [J].
Bauer, CM ;
Pinto, LH ;
Cross, TA ;
Lamb, RA .
VIROLOGY, 1999, 254 (01) :196-209
[7]   Rotational coupling of the transmembrane and kinase domains of the Neu receptor tyrosine kinase [J].
Bell, CA ;
Tynan, JA ;
Hart, KC ;
Meyer, AN ;
Robertson, SC ;
Donoghue, DJ .
MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (10) :3589-3599
[8]   Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: A new homology modeling tool [J].
Bower, MJ ;
Cohen, FE ;
Dunbrack, RL .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 267 (05) :1268-1282
[9]  
Bowie JU, 1999, PROTEIN SCI, V8, P2711
[10]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921