Ionic Interactions Promote Transmembrane Helix-Helix Association Depending on Sequence Context
Ionic Interactions Promote Transmembrane Helix-Helix Association Depending on Sequence Context
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DOI：
10.1016/j.jmb.2009.11.054
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发表时间：
2010-02-19
影响因子：
5.6
通讯作者：
Langosch, Dieter
中科院分区：
文献类型：
--
作者：
Herrmann, Jana R.;Fuchs, Angelika;Langosch, Dieter
膜蛋白的折叠和寡聚化常常依赖于跨膜螺旋的特异性相互作用。螺旋-螺旋界面的相互作用氨基酸可以形成复杂的基序并施加不同类型的分子力。在这里，一组强自我相互作用的跨膜结构域（TMD），从组合库中分离，被发现含有碱性和酸性残基，与极性不可电离的氨基酸和C-末端GxxxG基序的组合。选定的序列和重建高亲和力接口的突变分析证实了这些残基在同型相互作用的合作。探测异型相互作用表明存在螺旋间电荷-电荷相互作用。此外，一个简单的图案的电离残基和GxxxG显着过度在天然TMD，这些图案的特定组合表现出高亲和力的异型相互作用。我们得出结论，膜内电荷-电荷相互作用依赖于序列上下文。此外，他们似乎重要的同型和异型的相互作用，许多天然的TMDs。(C)2009爱思唯尔有限公司版权所有。
Folding and oligomerization of integral membrane proteins frequently depend on specific interactions of transmembrane helices. Interacting amino acids of helix-helix interfaces may form complex motifs and exert different types of molecular forces. Here, a set of strongly self-interacting transmembrane domains (TMDs), as isolated from a combinatorial library, was found to contain basic and acidic residues, in combination with polar nonionizable amino acids and C-terminal GxxxG motifs. Mutational analyses of selected sequences and reconstruction of high-affinity interfaces confirmed the cooperation of these residues in homotypic interactions. Probing heterotypic interaction indicated the presence of interhelical charge-charge interactions. Furthermore, simple motifs of an ionizable residue and GxxxG are significantly overrepresented in natural TMDs, and a specific combination of these motifs exhibits high-affinity heterotypic interaction. We conclude that intramembrane charge-charge interactions depend on sequence context. Moreover, they appear important for homotypic and heterotypic interactions of numerous natural TMDs. (C) 2009 Elsevier Ltd. All rights reserved.