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芳香-芳香相互作用驱动GA95和GB95（存在三个残基差异）的折叠转变。

Aromatic-aromatic interactions drive fold switch of GA95 and GB95 with three residue difference.

作者信息

Chen Chen, Zhang Zeting, Duan Mojie, Wu Qiong, Yang Minghui, Jiang Ling, Liu Maili, Li Conggang

机构信息

Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan National Laboratory for Optoelectronics, Wuhan Institute of Physics and Mathematics, Innovation Academy of Precision Measurement, Chinese Academy of Sciences Wuhan 430071 China

Graduate University of Chinese Academy of Sciences Beijing 100049 China.

出版信息

Chem Sci. 2024 Dec 18;16(4):1885-1893. doi: 10.1039/d4sc04951a. eCollection 2025 Jan 22.

DOI:10.1039/d4sc04951a
PMID:39720130
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11665817/
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.

摘要

蛋白质通常采用单一折叠结构来执行其功能，但具有多种折叠状态的变构蛋白却违背了这一规律。解析变构蛋白构象相互转换的机制具有挑战性。在此，我们利用核磁共振（NMR）、圆二色性（CD）和全原子分子动力学（MD）模拟来阐明GA95和GB95蛋白折叠转换的机制，这两种蛋白具有95%的序列同源性。结果表明，长程相互作用，特别是涉及F52、Y45、F30和Y29残基的芳香族π-π相互作用，对于蛋白质从3α折叠转变为4β + α折叠至关重要。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密码提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/7aec8a0c53c6/d4sc04951a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/ae1c7fbe1178/d4sc04951a-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/37a7bd903c48/d4sc04951a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/a1533bb93b4e/d4sc04951a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/e0c0657abe1b/d4sc04951a-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/7aec8a0c53c6/d4sc04951a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/ae1c7fbe1178/d4sc04951a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/2e75d2836914/d4sc04951a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/990e8e53080d/d4sc04951a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/37a7bd903c48/d4sc04951a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/a1533bb93b4e/d4sc04951a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/e0c0657abe1b/d4sc04951a-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5e/11752788/7aec8a0c53c6/d4sc04951a-f7.jpg

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本文引用的文献

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Function Switch of a Fungal Sesterterpene Synthase through Molecular Dynamics Simulation Assisted Alteration of an Aromatic Residue Cluster in the Active Pocket of PfNS.真菌甾体合酶功能的切换通过分子动力学模拟改变 PfNS 活性口袋中的芳香族残基簇
Angew Chem Int Ed Engl. 2024 Sep 9;63(37):e202406246. doi: 10.1002/anie.202406246. Epub 2024 Aug 12.
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Accurate structure prediction of biomolecular interactions with AlphaFold 3.利用 AlphaFold 3 进行生物分子相互作用的精确结构预测。
Nature. 2024 Jun;630(8016):493-500. doi: 10.1038/s41586-024-07487-w. Epub 2024 May 8.
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High-throughput prediction of protein conformational distributions with subsampled AlphaFold2.
利用 AlphaFold2 的子采样进行蛋白质构象分布的高通量预测。
Nat Commun. 2024 Mar 27;15(1):2464. doi: 10.1038/s41467-024-46715-9.
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Metamorphic proteins and how to find them.变形蛋白及其寻找方法。
Curr Opin Struct Biol. 2024 Jun;86:102807. doi: 10.1016/j.sbi.2024.102807. Epub 2024 Mar 26.
5
Predicting multiple conformations via sequence clustering and AlphaFold2.通过序列聚类和AlphaFold2预测多种构象
Nature. 2024 Jan;625(7996):832-839. doi: 10.1038/s41586-023-06832-9. Epub 2023 Nov 13.
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Unraveling the roles of aromatic cluster side-chain interactions on the structural stability and functional significance of psychrophilic Sphingomonas sp. glutaredoxin 3.解析芳香簇侧链相互作用在嗜冷鞘氨醇单胞菌谷氧还蛋白 3 的结构稳定性和功能意义中的作用。
PLoS One. 2023 Aug 31;18(8):e0290686. doi: 10.1371/journal.pone.0290686. eCollection 2023.
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Fluid protein fold space and its implications.流体蛋白质折叠空间及其意义。
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Identification of a covert evolutionary pathway between two protein folds.鉴定两种蛋白质折叠之间的隐蔽进化途径。
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