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The AAA + ATP ase TRIP 13 remodels HORMA domains through N‐terminal engagement and unfolding
Author(s) -
Ye Qiaozhen,
Kim Dong Hyun,
Dereli Ihsan,
Rosenberg Scott C,
Hagemann Goetz,
Herzog Franz,
Tóth Attila,
Cleveland Don W,
Corbett Kevin D
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797291
Subject(s) - terminal (telecommunication) , biology , microbiology and biotechnology , computer science , computer network
Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD 2 and the meiotic HORMAD s, assemble into signaling complexes by binding short peptides termed “closure motifs”. The AAA + ATP ase TRIP 13 regulates both MAD 2 and meiotic HORMAD s 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 TRIP 13 recognizes MAD 2 with the help of the adapter protein p31 comet . We show that p31 comet binding to the TRIP 13 N‐terminal domain positions the disordered MAD 2 N‐terminus for engagement by the TRIP 13 “pore loops”, which then unfold MAD 2 in the presence of ATP . N‐terminal truncation of MAD 2 renders it refractory to TRIP 13 action in vitro , and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP 13 function. Similar truncation of HORMAD 1 in mouse spermatocytes compromises its TRIP 13‐mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP 13.