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Assembly of transmembrane helices of simple polytopic membrane proteins from sequence conservation patterns
Author(s) -
Park Yungki,
Helms Volkhard
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21025
Subject(s) - bacteriorhodopsin , helix bundle , rhodopsin , crystallography , helix (gastropod) , transmembrane domain , sequence (biology) , protein structure , transmembrane protein , chemistry , membrane protein , biology , membrane , biochemistry , retinal , ecology , receptor , snail
The transmembrane (TM) domains of most membrane proteins consist of helix bundles. The seemingly simple task of TM helix bundle assembly has turned out to be extremely difficult. This is true even for simple TM helix bundle proteins, i.e., those that have the simple form of compact TM helix bundles. Herein, we present a computational method that is capable of generating native‐like structural models for simple TM helix bundle proteins having modest numbers of TM helices based on sequence conservation patterns. Thus, the only requirement for our method is the presence of more than 30 homologous sequences for an accurate extraction of sequence conservation patterns. The prediction method first computes a number of representative well‐packed conformations for each pair of contacting TM helices, and then a library of tertiary folds is generated by overlaying overlapping TM helices of the representative conformations. This library is scored using sequence conservation patterns, and a subsequent clustering analysis yields five final models. Assuming that neighboring TM helices in the sequence contact each other (but not that TM helices A and G contact each other), the method produced structural models of Cα atom root‐mean‐square deviation (CA RMSD) of 3–5 Å from corresponding crystal structures for bacteriorhodopsin, halorhodopsin, sensory rhodopsin II, and rhodopsin. In blind predictions, this type of contact knowledge is not available. Mimicking this, predictions were made for the rotor of the V‐type Na + ‐adenosine triphosphatase without such knowledge. The CA RMSD between the best model and its crystal structure is only 3.4 Å, and its contact accuracy reaches 55%. Furthermore, the model correctly identifies the binding pocket for sodium ion. These results demonstrate that the method can be readily applied to ab initio structure prediction of simple TM helix bundle proteins having modest numbers of TM helices. Proteins 2006. © 2006 Wiley‐Liss, Inc.