内在无序蛋白的相关片段作为同型相分离的驱动因素。

IF 8.7 Q1 CHEMISTRY, MULTIDISCIPLINARY
JACS Au Pub Date : 2025-08-21 eCollection Date: 2025-09-22 DOI:10.1021/jacsau.5c00733
Huan-Xiang Zhou
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引用次数: 0

摘要

许多研究表明,决定内在无序蛋白(IDPs)相分离的是氨基酸组成,而不是它们在序列上的位置。特别是芳香氨基酸和精氨酸已被确定为主要驱动因素。在这里,我强调了氨基酸在相分离中沿序列的位置的重要性。具体来说,易相互作用的氨基酸簇,包括色氨酸和精氨酸,沿着序列形成相关片段,这些相关片段,而不是单个残基,驱动许多IDPs的相分离。相关片段表现为跨越主干15N NMR横向弛豫率主要峰的残基延伸,可以通过称为SeqDYN的基于序列的方法来预测(https://zhougroup-uic.github.io/SeqDYNidp/)。单个残基之间的链间相互作用可能过于短暂,但涉及多个残基的相关片段之间的相互作用可以提供相分离所需的强度。事实上,核磁共振和其他技术揭示的序列基序对相分离很重要,经常映射到seqdyn预测的相关片段。包括CAPRIN1的G624-R626、G638-R640和R660-Q666残基,laf1的R21-G30残基,FUS的Q9-P21残基。SeqDYN提出了一种基于序列的方法来识别驱动IDPs相分离的基序。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Correlated Segments of Intrinsically Disordered Proteins as Drivers of Homotypic Phase Separation.

Correlated Segments of Intrinsically Disordered Proteins as Drivers of Homotypic Phase Separation.

Correlated Segments of Intrinsically Disordered Proteins as Drivers of Homotypic Phase Separation.

Correlated Segments of Intrinsically Disordered Proteins as Drivers of Homotypic Phase Separation.

Many studies have suggested that amino acid composition, not their positions along the sequence, is the determinant of phase separation of intrinsically disordered proteins (IDPs). In particular, aromatic amino acids and Arg have been identified as major drivers. Here I underscore the importance of the positions of amino acids along the sequence in phase separation. Specifically, clusters of interaction-prone amino acids, including Trp and Arg, along the sequence form correlated segments, and these correlated segments, rather than individual residues, drive the phase separation of many IDPs. Correlated segments manifest themselves as stretches of residues that span major peaks in the backbone 15N NMR transverse relaxation rates and can be predicted by a sequence-based method called SeqDYN (https://zhougroup-uic.github.io/SeqDYNidp/). Interchain interactions between individual residues may be too transient, but those between correlated segments involve multiple residues can provide the strengths required for phase separation. Indeed, sequence motifs revealed by NMR and other techniques as important for phase separation frequently map to SeqDYN-predicted correlated segments. These include residues G624-R626, G638-R640, and R660-Q666 of CAPRIN1, residues R21-G30 of LAF-1, and residues Q9-P21 of FUS. SeqDYN presents a sequence-based method for identifying motifs that drive phase separation of IDPs.

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