The LC8 Recognition Motif Preferentially Samples Polyproline II Structure in Its Free State.
The LC8 Recognition Motif Preferentially Samples Polyproline II Structure in Its Free State.
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LC8 识别基序优先采样游离态的聚脯氨酸 II 结构。
DOI：
10.1021/acs.biochem.7b00552
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发表时间：
2017
期刊：
影响因子：
2.9
通讯作者：
Barbar,Elisar
中科院分区：
文献类型：
--
作者：
Morgan,JessicaL;Jensen,MaleneRingkjøbing;Ozenne,Valéry;Blackledge,Martin;Barbar,Elisar
LC 8是一种普遍存在的枢纽蛋白，它结合内在无序的蛋白质并促进它们组装成更高阶的复合物。在100多种必需的LC 8结合蛋白中的共同特征是在10-12个氨基酸的识别序列中存在保守的QT基序，但在QT对的N-和C-末端存在可变的氨基酸。LC 8结合伴侣之间的序列多样性意味着结构因素也有助于特异性。为了研究是否有这样一个因素是LC 8结合序列所支持的瞬时二级结构，我们在这里报告了ICTL的分子系综描述，ICTL是动力蛋白中间链的一个结构域，包括轻链LC 8和Tctex 1的结合位点。核磁共振二次化学位移和残留偶极耦合值与合奏生成和选择算法相结合，表明偏离统计（随机）线圈行为与升高的人口聚脯氨酸II（PPII）的构象ICTL区域结合LC 8和Tctex 1。一个和三个键标量耦合的独立测量确认PPII瞬态二级结构倾向。鉴于在IC/Tctex 1/LC 8三元复合物中，ICTL在Tctex 1和LC 8的界面处形成β链，我们假设PPII构象可能有助于其初始对接和插入β折叠LC 8二聚体界面的结合裂缝中。分子系综计算内在无序的LC 8结合伙伴也揭示PPII构象内和接近LC 8识别基序的采样，这表明一个PPII构象的偏好是一般的LC 8结合伙伴。
LC8 is a ubiquitous hub protein that binds intrinsically disordered proteins and promotes their assembly into higher-order complexes. A common feature among the more than 100 essential LC8 binding proteins is that in the 10–12-amino acid recognition sequence there is a conserved QT motif but variable amino acids N- and C-terminal to the QT pair. The sequence diversity among LC8 binding partners implies that structural factors also contribute to specificity. To investigate whether one such factor is the transient secondary structure favored by an LC8 binding sequence, we report here a molecular ensemble description of ICTL, a domain of the dynein intermediate chain that includes binding sites for light chains LC8 and Tctex1. Nuclear magnetic resonance secondary chemical shifts and residual dipolar coupling values combined with ensemble generation and selection algorithms indicate a deviation from statistical (random) coil behavior with an elevated population of polyproline II (PPII) conformations for the ICTLregions that bind LC8 and Tctex1. Independent measurements of one- and three-bond scalar couplings confirm the PPII transient secondary structure propensity. Given that in the IC/Tctex1/LC8 ternary complex ICTLforms a β-strand at the interface of Tctex1 and LC8, we hypothesize that a PPII conformation may facilitate its initial docking and insertion into the binding cleft of the β-sheet LC8 dimer interface. Molecular ensemble calculations for intrinsically disordered LC8 binding partners also reveal PPII conformational sampling within and proximate to the LC8 recognition motifs, suggesting that a preference for a PPII conformation is general for LC8 binding partners.
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影响因子：
15
作者：
Cho, Min-Kyu;Kim, Hai-Young;Zweckstetter, Markus
通讯作者：
Zweckstetter, Markus
DOI：
10.1073/pnas.0510549103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Makowska, J;Rodziewicz-Motowidlo, S;Scheraga, HA
通讯作者：
Scheraga, HA
影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
15
作者：
Salmon, Loic;Nodet, Gabrielle;Blackledge, Martin
通讯作者：
Blackledge, Martin
影响因子：
2.9
作者：
Barbar, Elisar
通讯作者：
Barbar, Elisar