Influence of sequence length and charged residues on Swc5 binding with histone H2A-H2B
Influence of sequence length and charged residues on Swc5 binding with histone H2A-H2B
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DOI：
10.1002/prot.26035
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发表时间：
2020-12-23
影响因子：
2.9
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Chu, Wen-Ting;Wang, Jin
SWR是染色质重塑蛋白家族的成员，参与组蛋白H2 A被H2A.Z取代。SWR亚基之一Swc 5具有固有无序区域并结合H2 A-H2 B二聚体。尽管Swc 5与H2 A-H2 B的结合结构已被解析，但研究Swc 5与H2 A-H2 B之间的结合机制以及电荷相互作用的作用仍然具有挑战性。在这里，我们开发了一个粗粒度的结构为基础的模型，并进行分子动力学模拟，以研究具有不同长度的两个Swc 5区域（swc 5-a和swc 5-B）与H2 A-H2 B的结合过程。模拟结果表明，SWC 5-a/SWC 5-B和H2 A-H2 B之间的静电相互作用对结合的影响不同. swc 5-a/swc 5-B与H2 A-H2 B之间的静电相互作用不仅可以加速结合的初始捕获步骤，而且可以将swc 5-a/swc 5-B捕获在H2 A上的错误结合位点。此外，Swc 5保守的DEF/Y-2基序对于在初始步骤中与H2 A-H2 B的结合亲和力和识别是重要的。swc 5-a和swc 5-B在达到最终结合态之前都经历结构转变。该理论研究提供了swc 5-a/swc 5-B和H2 A-H2 B结合过程的重要细节和潜在的物理机制。
SWR is a member of chromatin remodeler family and participates the replacement of histone H2A with H2A.Z. One of the SWR subunits, Swc5, has an intrinsically disordered region and binds to H2A-H2B dimer. Though the binding structure of Swc5 and H2A-H2B has been resolved recently, it is still challenging to investigate the binding mechanism as well as the role of the charge interactions between Swc5 and H2A-H2B. Here we developed a coarse-grained structure-based model and performed molecular dynamics simulations to investigate the binding processes of two Swc5 regions with different lengths (swc5-a and swc5-b) to H2A-H2B. The simulation results suggest a different role of electrostatic interactions between swc5-a/swc5-b and H2A-H2B on binding. The electrostatic interactions between swc5-a/swc5-b and H2A-H2B can not only accelerate the initial capture step of binding, but can also trap the swc5-a/swc5-b at the wrong binding site on H2A. Besides, the conserved DEF/Y-2 motif of Swc5 is important for the binding affinity and the recognition with H2A-H2B at the initial step. Both swc5-a and swc5-b undergo a structural shift before reaching the final bound state. This theoretical study provides important details and the underlying physical mechanisms of the binding processes of swc5-a/swc5-b and H2A-H2B.