Aromatic–aromatic interactions drive fold switch of GA95 and GB95 with three residue difference†

IF 7.6 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Chen Chen, Zeting Zhang, Mojie Duan, Qiong Wu, Minghui Yang, Ling Jiang, Maili Liu and Conggang Li
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引用次数: 0

Abstract

Proteins typically adopt a single fold to carry out their function, but metamorphic proteins, with multiple folding states, defy this norm. Deciphering the mechanism of conformational interconversion of metamorphic proteins is challenging. Herein, we employed nuclear magnetic resonance (NMR), circular dichroism (CD), and all-atom molecular dynamics (MD) simulations to elucidate the mechanism of fold switching in proteins GA95 and GB95, which share 95% sequence homology. The results reveal that long-range interactions, especially aromatic π–π interactions involving residues F52, Y45, F30, and Y29, are critical for the protein switching from a 3α to a 4β + α fold. This study contributes to understanding how proteins with highly similar sequences fold into distinct conformations and may provide valuable insights into the protein folding code.

Abstract Image

芳香-芳香相互作用驱动GA95和GB95的三残差折叠开关
蛋白质通常采用单一折叠来执行其功能,但具有多种折叠状态的变质蛋白质违背了这一规范。破译变形蛋白的构象相互转化机制是一项具有挑战性的工作。本文采用核磁共振(NMR)、圆二色性(CD)和全原子分子动力学(MD)模拟来阐明GA95和GB95蛋白的折叠切换机制,这两个蛋白具有95%的序列同源性。结果表明,远程相互作用,特别是芳香π-π相互作用涉及残基F52, Y45, F30和Y29,是蛋白质从3α转换到4β+α折叠的关键。这项研究有助于理解具有高度相似序列的蛋白质如何折叠成不同的构象,并可能为蛋白质折叠代码提供有价值的见解。
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来源期刊
Chemical Science
Chemical Science CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
14.40
自引率
4.80%
发文量
1352
审稿时长
2.1 months
期刊介绍: Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.
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