The interplay of ligand binding and quaternary structure in the diverse interactions of dynein light chain LC8.
The interplay of ligand binding and quaternary structure in the diverse interactions of dynein light chain LC8.
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DOI：
10.1016/j.jmb.2008.09.083
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发表时间：
2008-12-26
影响因子：
5.6
通讯作者：
Barbar, Elisar
中科院分区：
文献类型：
--
作者：
Benison, Gregory;Karplus, P. Andrew;Barbar, Elisar
动力蛋白轻链LC 8是一种小的、二聚体的、非常高度保守的球状蛋白，是动力蛋白和肌球蛋白分子马达的组成部分，但似乎在与分子马达无关的多种蛋白质复合物中具有更广泛的作用。LC 8结合两个家族的靶标：具有KXTQT序列指纹的那些和具有GIQVD指纹的那些。所有已知的LC 8结合伙伴含有这些指纹共享一个共同的结合位点的LC 8提出的问题是什么决定结合特异性。在这里，我们提出的晶体结构的载脂蛋白-LC 8在1.7-ε分辨率，其中，当与几个LC 8复合物的晶体结构相比，深入了解LC 8的结合多样性的机制。肽结合与四级结构的转变有关，四级结构的转变扩大了配体可用的疏水结合表面，此外还改变了三级结构和结合沟周围LC 8的排序。所观察到的四级位移表明，在两个相同的网站之一的结合可以影响在其他结合的机制。从每个指纹家族的肽滴定的NMR光谱显示两个结合位点之间的变构相互作用的证据，在两个配体家族的不同程度。结合位点之间的变构相互作用可能是促进来自同一家族的配体同时结合的机制，为两个指纹提供生理作用。
Dynein light chain LC8 is a small, dimeric, and very highly conserved globular protein that is an integral part of the dynein and myosin molecular motors but appears to have a broader role in multiple protein complexes unrelated to molecular motors. LC8 binds to two families of targets: those having a KXTQT sequence fingerprint and those having a GIQVD fingerprint. All known LC8 binding partners containing these fingerprints share a common binding site on LC8 that raises the question of what determines binding specificity. Here, we present the crystal structure of apo-LC8 at 1.7-Å resolution, which, when compared with the crystal structures of several LC8 complexes, gives insight into the mechanism underlying the binding diversity of LC8. Peptide binding is associated with a shift in quaternary structure that expands the hydrophobic binding surface available to the ligand, in addition to changes in tertiary structure and ordering of LC8 around the binding groove. The observed quaternary shift suggests a mechanism by which binding at one of the two identical sites can influence binding at the other. NMR spectra of titrations with peptides from each fingerprint family show evidence of allosteric interaction between the two binding sites, to a differing degree in the two ligand families. Allosteric interaction between the binding sites may be a mechanism to promote simultaneous binding of ligands from the same family, providing a physiological role for the two fingerprints.
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影响因子：
5.6
作者：
Fan, JS;Zhang, Q;Zhang, MJ
通讯作者：
Zhang, MJ
DOI：
10.1107/s090744499900846x
发表时间：
1999-10-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Leslie, AGW
通讯作者：
Leslie, AGW
影响因子：
64.8
作者：
CHOTHIA, C;JANIN, J
通讯作者：
JANIN, J
DOI：
10.1002/prot.10286
发表时间：
2003-02-15
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Lovell, SC;Davis, IW;Richardson, DC
通讯作者：
Richardson, DC
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A