美国加州大学伯克利分校Michael Rape课题组近日取得一项新成果。经过不懈努力，他们揭示了二聚体质量控制的结构基础。相关论文于2020年8月19日在线发表于国际学术期刊《自然》杂志上。
研究人员提供了SCF–FBXL17（一种二聚体质量控制的E3连接酶）对靶标蛋白选择的结构基础，该酶通过泛素化并降解BTB蛋白的非活性异二聚体，同时保留功能性同二聚体。 研究人员发现SCF–FBXL17破坏了异常的BTB二聚体，这些二聚体未能稳定BTB结构域中围绕高度分散β链的分子间β-折叠。复合物解离使SCF–FBXL17可以包裹单个BTB结构域，从而导致强泛素化。因此，SCF–FBXL17可以探测BTB结构域的形状和互补性，该机制非常适用于重复发生相互作用模块复合物组成的质量控制。
据了解，大多数质量控制途径都针对错误折叠的蛋白质，以防止毒性聚集和神经变性。二聚体质量控制通过消除异常组成的复合物进一步改善蛋白质稳态，但是该系统如何检测不正确的亚基仍然未知。
附：英文原文
Title: Structural basis for dimerization quality control
Author: Elijah L. Mena, Predrag Jevti, Basil J. Greber, Christine L. Gee, Brandon G. Lew, David Akopian, Eva Nogales, John Kuriyan, Michael Rape
Issue&Volume: 2020-08-19
Abstract: Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration1. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition2, but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF–FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF–FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCF–FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF–FBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules. Structural studies of the dimerization quality control E3 ubiquitin ligase SCF–FBXL17 indicate that its selectivity for aberrant complex formation is based on recognizing both shape and complementarity of interacting domains.
DOI: 10.1038/s41586-020-2636-7
Source: https://www.nature.com/articles/s41586-020-2636-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
