Grup de Recerca en Bioinformàtica i Estadística Mèdica, Departament de Biologia de Sistemes, Escola Politècnica Superior, Universitat de Vic, 08500 Vic, Barcelona, Catalonia, Spain.
Bioinformatics. 2013 Jul 1;29(13):1589-92. doi: 10.1093/bioinformatics/btt249. Epub 2013 May 14.
Integral polytopic membrane proteins contain only two types of folds in their transmembrane domains: α-helix bundles and β-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.
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 Å). Moreover, a large group of β-barrel pairs with low-sequence identity (<20%) still maintain a close structural similarity (rmsd < 2.5 Å). 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.
Supplementary data are available at Bioinformatics online.
整联蛋白多拓扑膜蛋白在其跨膜域中仅包含两种折叠类型：α-螺旋束和β-桶。越来越多的这些蛋白质的晶体结构可用于初步估计序列变异性如何影响其跨膜域中的结构保守性。因此，我们旨在确定维持与脂质双层疏水性相容的跨膜分子结构所需的成对序列同一性。
均方根偏差（rmsd）和序列同一性是从具有相同折叠的同源多拓扑膜蛋白对的结构比对中计算得出的。对这些数据的分析表明，在所谓的“暮光区”（20-35%）中具有序列同一性的跨膜片段对显示出高度的结构相似性（rmsd<1.5 Å）。此外，大量具有低序列同一性（<20%）的β-桶对仍保持密切的结构相似性（rmsd<2.5 Å）。因此，我们得出结论，跨膜区域的折叠保存需要比球状蛋白更少的序列保守性。这些发现对进化相关膜蛋白的同源建模具有直接影响。
补充数据可在Bioinformatics 在线获得。
