钙结合蛋白S100A1以ph依赖的方式与titin的N2A插入序列结合。

IF 3.3 2区 医学 Q1 PHYSIOLOGY
Journal of General Physiology Pub Date : 2025-01-06 Epub Date: 2024-12-31 DOI:10.1085/jgp.202313472
Sabrina I Apel, Emily Schaffter, Nicholas Melisi, Matthew J Gage
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引用次数: 0

摘要

肌粘连蛋白是肌节中的第三条收缩丝,它在肌节的完整性和被动张力和主动张力中起着至关重要的作用。与粗丝和细丝不同,细丝分别是肌凝蛋白和肌动蛋白的聚合物,肌凝蛋白是从z -盘到m -线的单个蛋白质。titin内的N2A区域已被确定为肌肉的信号中枢,并被证明参与多种相互作用。N2A区域内的插入序列(UN2A)被预测为Ca2+结合蛋白S100A1的潜在结合位点。我们使用尺寸排除色谱,表面等离子体共振和荧光共振能量转移的组合证明S100A1可以结合到UN2A区域。我们进一步证明,这种相互作用发生在钙与S100A1结合的条件下,这表明当钙结合时S100A1的构象变化是重要的。我们还观察到UN2A的构象变化是由pH的变化引起的,这表明UN2A的构象灵活性在与S100A1的相互作用中起关键作用。这些结果使我们提出S100A1和UN2A的相互作用可能作为一种传感器来调节titin的功能,以响应肌肉的生理变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The calcium-binding protein S100A1 binds to titin's N2A insertion sequence in a pH-dependent manner.

Titin is the third contractile filament in the sarcomere, and it plays a critical role in sarcomere integrity and both passive and active tension. Unlike the thick and thin filaments, which are polymers of myosin and actin, respectively, titin is a single protein that spans from Z-disk to M-line. The N2A region within titin has been identified as a signaling hub for the muscle and is shown to be involved in multiple interactions. The insertion sequence (UN2A) within the N2A region was predicted as a potential binding site for the Ca2+-binding protein, S100A1. We demonstrate using a combination of size exclusion chromatography, surface plasmon resonance, and fluorescence resonance energy transfer that S100A1 can bind to the UN2A region. We further demonstrate that this interaction occurs under conditions where calcium is bound to S100A1, suggesting that the conformational shift in S100A1 when calcium binds is important. We also observed a conformational change in UN2A induced by shifts in pH, suggesting that conformational flexibility in UN2A plays a critical role in the interaction with S100A1. These results lead us to propose that the interaction of S100A1 and UN2A might act as a sensor to regulate titin's function in response to physiological changes in the muscle.

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来源期刊
CiteScore
6.00
自引率
10.50%
发文量
88
审稿时长
6-12 weeks
期刊介绍: General physiology is the study of biological mechanisms through analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization. The mission of Journal of General Physiology (JGP) is to publish mechanistic and quantitative molecular and cellular physiology of the highest quality, to provide a best-in-class author experience, and to nurture future generations of independent researchers. The major emphasis is on physiological problems at the cellular and molecular level.
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