When a module is also a domain: The role of the N terminus in the stability and the dynamics of immunoglobulin domains from titin
When a module is also a domain: The role of the N terminus in the stability and the dynamics of immunoglobulin domains from titin
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DOI：
10.1006/jmbi.1996.0725
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发表时间：
1997-01-17
影响因子：
5.6
通讯作者：
Pastore, A
中科院分区：
文献类型：
--
作者：
Pfuhl, M;Improta, S;Pastore, A
titin是一种来自肌肉的巨大模块蛋白，在对其结构研究的过程中，我们报道了来自titin的免疫球蛋白样结构域（igg -like）的n端延伸可以稳定这种折叠。为了研究这种效应的结构基础，我们已经解决了NEXTM5的结构，它在M5的序列上添加了6个氨基酸，这是一个以前已经实现完整结构确定的结构域。在本工作中，根据M5和NEXTM5和其他titin结构域收集的数据，比较了它们的结构和动力学。在NEXTM5中，添加的六个残基中有三个是结构化的，并且与附近的BC和FG环相邻。结果，与B链形成了三个新的主氢键，使a链延长了两个残基，并减少了环的暴露表面积。涉及侧链的额外接触引起了稳定性的显著的pH依赖性。有趣的是，在核磁共振时间尺度上，扩展域的整体动力学与其增加的稳定性之间没有观察到相关性。这两种结构之间最明显的区别是在N端附近，它在延伸时变得更加刚性。由于在免疫球蛋白i集的其他区域观察到类似的接触模式，因此我们的结果与该蛋白家族具有普遍相关性。我们的工作也可能启发一个更合理的方法来研究领域边界及其对模块稳定性的影响。(C) 1997学术出版社有限公司
In the course of a structural study of titin, a giant modular protein from muscle, we have reported that N-terminal extension of immunoglobulin-like (Ig-like) domains from titin stabilizes this fold. In order to investigate the structural basis of such an effect, we have solved the structure of NEXTM5, which has six amino acids added to the sequence of M5, a domain for which full structure determination has been previously achieved. In the present work, the structures and the dynamics of M5 and NEXTM5 are compared in the light of data collected for these and other titin domains. In NEXTM5, three out of the six added residues are structured and pack against the nearby BC and FG loops. As a consequence, three new backbone hydrogen bonds are formed with the B strand, extending the A strand by two residues and decreasing the exposed surface area of the loops. Additional contacts which in involve the side-chains give rise to a remarkable pH dependence of the stability. Interestingly, no correlation is observed on the NMR time-scale between the overall dynamics of the extended domain and its increased stability. The most noticeable differences between the two constructs are localised around the N terminus, which becomes more rigid upon extension. Since a similar pattern of contacts is observed for other domains of the immunoglobulin I-set, our results are of general relevance for this protein family. Our work might also inspire a more rational approach to the investigation of domain boundaries and their influence on module stability. (C) 1997 Academic Press Limited