5VQA

Structure of human TRIP13, ATP-bound form

5VQA の概要

• エントリーDOI: 10.2210/pdb5vqa/pdb
• 関連するPDBエントリー: 5VQ9
• 分子名称: Pachytene checkpoint protein 2 homolog, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: aaa+ atpase, meiosis, spindle assembly checkpoint, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49113.84

構造登録者

Ye, Q.,Corbett, K.D. (登録日: 2017-05-08, 公開日: 2017-06-14, 最終更新日: 2023-10-04)

主引用文献

Ye, Q.,Kim, D.H.,Dereli, I.,Rosenberg, S.C.,Hagemann, G.,Herzog, F.,Toth, A.,Cleveland, D.W.,Corbett, K.D.
The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding.
EMBO J., 36:2419-2434, 2017

PubMed Abstract: Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed "closure motifs". The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain-closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31 We show that p31 binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 "pore loops", which then unfold MAD2 in the presence of ATP N-terminal truncation of MAD2 renders it refractory to TRIP13 action , and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain-closure motif complexes by TRIP13.

PubMed: 28659378
DOI: 10.15252/embj.201797291

実験手法

X-RAY DIFFRACTION (2.54 Å)