The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding.

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^comet We show that p31^comet 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 truncatio

SUBMITTER: Ye Q 

PROVIDER: S-EPMC5556265 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature