人类 Golm1 卷曲螺旋结构域的第一个结构揭示了一个意想不到的四聚体,并突出了其结构多样性。
The first structure of human Golm1 coiled coil domain reveals an unexpected tetramer and highlights its structural diversity.
发表日期:2024 Jul 02
作者:
Wenfeng Bai, Bowen Li, Pei Wu, Xinzhu Li, Xiaochen Huang, Ning Shi, Congcong Yang, Fen Hu, Xi Xie
来源:
Int J Biol Macromol
摘要:
高尔基膜蛋白 1 (Golm1) 是一种具有多种亚细胞定位的跨膜蛋白,由于其与肝病和多种癌症的发生和进展密切相关,近年来引起了人们的广泛关注。有趣的是,虽然Golm1是一种膜蛋白,但含有卷曲螺旋结构域和柔性酸性区域的Golm1 C端也可以在各种肝病患者的血浆中检测到。值得注意的是,血清 Golm1 的卷曲螺旋结构域被认为在生理和病理功能中发挥着关键作用。然而,目前人们对这个卷曲螺旋结构域和全长蛋白的结构知之甚少,这可能限制了我们对Golm1的理解。因此,本研究旨在解决这一知识空白,并以 2.28Å 的分辨率报告了 Golm1 卷曲线圈域的第一个晶体结构。同时,我们还证实了Golm1卷曲螺旋结构域在溶液中可以形成四聚体。我们的结果表明,Golm1 可以形成一种新颖的四聚体结构,与之前报道的 Golm1 可以组装的二聚体结构不同,这可能为生理功能和病理作用的多样性提供新的见解。版权所有 © 2024。由 Elsevier B.V. 出版。
Golgi membrane protein 1 (Golm1), a transmembrane protein with diverse subcellular localizations, has garnered significant attention in recent years due to its strong association with the development and progression of liver diseases and numerous cancers. Interestingly, although Golm1 is a membrane protein, the C-terminal of Golm1, which contains a coiled coil domain and a flexible acid region, can also be detected in the plasma of patients with various liver diseases. Notably, the coiled coil domain of serum Golm1 is postulated to play a pivotal role in physiological and pathological functions. However, little is currently known about the structure of this coiled coil domain and the full-length protein, which may limit our understanding of Golm1. Therefore, this study aims to address this gap in knowledge and reports the first crystal structure of the coiled coil domain of Golm1 at a resolution of 2.28 Å. Meanwhile, we have also confirmed that the Golm1 coiled coil domain in solution can form tetramer. Our results reveal that Golm1 can form a novel tetrameric structure that differs from the previous reported dimeric structure Golm1 could assemble, which may provide novel insights into the diversity of physiological functions and pathological roles.Copyright © 2024. Published by Elsevier B.V.