Helical packing patterns in membrane and soluble proteins
Helical packing patterns in membrane and soluble proteins
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DOI：
10.1529/biophysj.104.049288
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Honig, B
中科院分区：
文献类型：
--
作者：
Gimpelev, M;Forrest, LR;Honig, B
本文介绍了膜和可溶性蛋白质中螺旋-螺旋相互作用的详细分析结果。构建了已知结构的膜蛋白中相互作用的螺旋对的数据集，并使用结构比对算法来识别可溶性蛋白中与膜蛋白数据集中的螺旋对良好重叠的螺旋对。发现膜蛋白中的大多数螺旋对在可溶性蛋白中具有大量的结构同源物，尽管在某些情况下，主要涉及不规则螺旋，不存在密切的同源物。对两组蛋白质中相互作用的螺旋之间的几何关系的分析确定了螺旋长度、界面面积、堆积角度和多肽主链之间的距离的分布的一些差异。然而，与膜蛋白螺旋对结构同源的可溶性蛋白螺旋对的子集表现出与膜蛋白中观察到的分布相似的分布。膜蛋白螺旋中较大的平均界面尺寸和较小的最近距离距离似乎部分是由于丙氨酸和甘氨酸的相对富集，特别是作为 AxxxA 和 GxxxG 基序的组成部分。有人认为膜螺旋的平均堆积并不比可溶性蛋白质中的螺旋更紧密。他们只是能够更加接近彼此。这使得它们能够在更长的距离上相互作用，这反过来又可能促进它们在脂双层的大部分宽度上保持接触。膜和可溶性蛋白质中的一些螺旋对之间观察到的密切结构相似性表明，在可溶性蛋白质中观察到的堆积模式可能有助于膜蛋白的建模。此外，驱动膜和可溶性蛋白质中螺旋堆积的力的大小似乎没有根本差异，这表明通过突变表面残基使膜蛋白更可溶的策略可能会取得成功，至少在某些情况下是这样。
This article presents the results of a detailed analysis of helix-helix interactions in membrane and soluble proteins. A data set of interacting pairs of helices in membrane proteins of known structure was constructed and a structure alignment algorithm was used to identify pairs of helices in soluble proteins that superimpose well with pairs of helices in the membrane-protein data set. Most helix pairs in membrane proteins are found to have a significant number of structural homologs in soluble proteins, although in some cases, primarily involving irregular helices, no close homologs exist. An analysis of geometric relationships between interacting helices in the two sets of proteins identifies some differences in the distributions of helix length, interfacial area, packing angle, and distance between the polypeptide backbones. However, a subset of soluble-protein helix pairs that are close structural homologs to membrane-protein helix pairs exhibits distributions that mirror those observed in membrane proteins. The larger average interface size and smaller distance of closest approach seen for helices in membrane proteins appears due in part to a relative enrichment of alanines and glycines, particularly as components of the AxxxA and GxxxG motifs. It is argued that membrane helices are not on average more tightly packed than helices in soluble proteins; they are simply able to approach each other more closely. This enables them to interact over longer distances, which may in turn facilitate their remaining in contact over much of the width of the lipid bilayer. The close structural similarity seen between some pairs of helices in membrane and soluble proteins suggests that packing patterns observed in soluble proteins may be useful in the modeling of membrane proteins. Moreover, there do not appear to be fundamental differences between the magnitude of the forces that drive helix packing in membrane and soluble proteins, suggesting that strategies to make membrane proteins more soluble by mutating surface residues are likely to encounter success, at least in some cases.