Identification of the critical structural determinants of the EF-hand domain arrangements in calcium binding proteins
Identification of the critical structural determinants of the EF-hand domain arrangements in calcium binding proteins
复制标题
钙结合蛋白中 EF-hand 结构域排列的关键结构决定因素的鉴定
DOI：
10.1016/j.bbapap.2012.01.005
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发表时间：
2012-04-01
影响因子：
3.2
通讯作者：
Wei, Qun
中科院分区：
文献类型：
--
作者：
Feng, Ye-dan;Li, Jing;Wei, Qun
EF-hand钙结合蛋白（CaBPs）具有较强的序列同源性，但在结构和功能上存在较大差异。因此，尽管钙调蛋白（CaM）和钙调磷酸酶B （CNB）都由四个EF手组成，但它们的结构域排列却截然不同。CaM和CaM样蛋白具有扩展的结构，而CNB和CNB样蛋白具有更紧凑的结构。在这项研究中，我们对3个cam样蛋白和6个cnb样蛋白进行了结构比对和分子动力学（MD）模拟，并量化了它们不同的结构和动力学特征，以确定它们的序列如何指定它们的结构和动力学。对这些蛋白的EF2-EF3区域的比对显示，两组蛋白之间的一些残基（不限于EF2和EF3基序之间的连接体）不同。定制的反折叠方法，然后进行结构评估和MD模拟，确定了这些残基在确定蛋白质结构中的关键作用。确定两种不同EF-hand结构域排列的关键决定因素以及与其各自功能相关的不同动力学特征，有助于深入了解这些EF-hand cabp之间的序列、结构、动力学和功能之间的关系。爱思唯尔B.V.版权所有
EF-hand calcium binding proteins (CaBPs) share strong sequence homology, but exhibit great diversity in structure and function. Thus although calmodulin (CaM) and calcineurin B (CNB) both consist of four EF hands, their domain arrangements are quite distinct. CaM and the CaM-like proteins are characterized by an extended architecture, whereas CNB and the CNB-like proteins have a more compact form. In this study, we performed structural alignments and molecular dynamics (MD) simulations on 3 CaM-like proteins and 6 CNB-like proteins, and quantified their distinct structural and dynamical features in an effort to establish how their sequences specify their structures and dynamics. Alignments of the EF2-EF3 region of these proteins revealed that several residues (not restricted to the linker between the EF2 and EF3 motifs) differed between the two groups of proteins. A customized inverse folding approach followed by structural assessments and MD simulations established the critical role of these residues in determining the structure of the proteins. Identification of the critical determinants of the two different EF-hand domain arrangements and the distinct dynamical features relevant to their respective functions provides insight into the relationships between sequence, structure, dynamics and function among these EF-hand CaBPs. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.