Relation between sequence and structure in membrane proteins
Relation between sequence and structure in membrane proteins
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DOI：
10.1093/bioinformatics/btt249
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发表时间：
2013-07-01
期刊：
影响因子：
5.8
通讯作者：
Deupi, Xavier
中科院分区：
文献类型：
--
作者：
Olivella, Mireia;Gonzalez, Angel;Deupi, Xavier
动机：整合多位膜蛋白在其跨膜结构域中仅包含两种类型的折叠：α-螺旋束和β-桶。这些蛋白质的可用晶体结构的数量不断增加，允许序列变异性如何影响其跨膜结构域中的结构保守性的初步估计。因此，我们的目标是确定必要的成对序列的身份，以保持跨膜分子结构与疏水性的lipidbilayer.Results兼容：根均方差（rmsd）和序列的身份计算从同源的多位膜蛋白共享相同的倍对的结构比对。对这些数据的分析表明，在所谓的“模糊区”（20-35%）中具有序列同一性的跨膜片段对显示出高结构相似性（rmsd < 1.5埃）。此外，大量具有低序列同一性（< 20%）的β-桶对仍然保持紧密的结构相似性（rmsd < 2.5埃）。因此，我们得出结论，折叠保存在跨膜区需要较少的序列保守性比球状蛋白。这些发现对进化相关膜蛋白的同源性建模有直接影响。
Motivation: Integral polytopic membrane proteins contain only two types of folds in their transmembrane domains: alpha-helix bundles and beta-barrels. The increasing number of available crystal structures of these proteins permits an initial estimation of how sequence variability affects the structure conservation in their transmembrane domains. We, thus, aim to determine the pairwise sequence identity necessary to maintain the transmembrane molecular architectures compatible with the hydrophobic nature of the lipid bilayer.Results: Root-mean-square deviation (rmsd) and sequence identity were calculated from the structural alignments of pairs of homologous polytopic membrane proteins sharing the same fold. Analysis of these data reveals that transmembrane segment pairs with sequence identity in the so-called 'twilight zone' (20-35%) display high-structural similarity (rmsd < 1.5 angstrom). Moreover, a large group of beta-barrel pairs with low-sequence identity (< 20%) still maintain a close structural similarity (rmsd < 2.5 angstrom). Thus, we conclude that fold preservation in transmembrane regions requires less sequence conservation than for globular proteins. These findings have direct implications in homology modeling of evolutionary-related membrane proteins.