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TRIP13是一种蛋白质重塑的AAA+ATP酶，可催化MAD2构象转换。

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.

作者信息

Ye Qiaozhen, Rosenberg Scott C, Moeller Arne, Speir Jeffrey A, Su Tiffany Y, Corbett Kevin D

机构信息

Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States.

National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.

出版信息

Elife. 2015 Apr 28;4:e07367. doi: 10.7554/eLife.07367.

DOI:10.7554/eLife.07367
PMID:25918846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4439613/
Abstract

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

摘要

AAA+ 家族ATP酶TRIP13是减数分裂重组和纺锤体组装检查点的关键调节因子，作用于保守的HORMA结构域家族的信号蛋白。本文我们展示了秀丽隐杆线虫TRIP13直系同源物PCH-2的结构，揭示了一个新的AAA+ ATP酶蛋白重塑酶家族。PCH-2拥有一个与蛋白重塑酶NSF和p97的底物识别结构域相关的底物识别结构域，而其整体六聚体结构和可能的结构机制与细菌蛋白解折叠酶ClpX极为相似。我们发现，在衔接蛋白p31(comet)的辅助下，TRIP13将HORMA家族纺锤体检查点蛋白MAD2从有信号活性的“封闭”构象转变为无活性的“开放”构象。我们提出，TRIP13和p31(comet)通过MAD2构象转换和有丝分裂检查点复合物的解体协同作用，使纺锤体组装检查点失活。一种类似的HORMA蛋白解体活性可能是TRIP13在减数分裂染色体结构和重组中关键调节功能的基础。

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