5WC2

Crystal Structure of ADP-bound human TRIP13

Summary for 5WC2

• Entry DOI: 10.2210/pdb5wc2/pdb
• Descriptor: Pachytene checkpoint protein 2 homolog, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: trip13, atpase, spindle assembly checkpoint, mad2, p31comet, cell cycle
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 48976.81

Authors

Jeong, B.-C.,Luo, X. (deposition date: 2017-06-29, release date: 2018-04-25, Last modification date: 2023-10-04)

Primary citation

Brulotte, M.L.,Jeong, B.C.,Li, F.,Li, B.,Yu, E.B.,Wu, Q.,Brautigam, C.A.,Yu, H.,Luo, X.
Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing.
Nat Commun, 8:1956-1956, 2017

PubMed Abstract: The spindle checkpoint maintains genomic stability and prevents aneuploidy. Unattached kinetochores convert the latent open conformer of the checkpoint protein Mad2 (O-Mad2) to the active closed conformer (C-Mad2), bound to Cdc20. C-Mad2-Cdc20 is incorporated into the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C). The C-Mad2-binding protein p31 and the ATPase TRIP13 promote MCC disassembly and checkpoint silencing. Here, using nuclear magnetic resonance (NMR) spectroscopy, we show that TRIP13 and p31 catalyze the conversion of C-Mad2 to O-Mad2, without disrupting its stably folded core. We determine the crystal structure of human TRIP13, and identify functional TRIP13 residues that mediate p31-Mad2 binding and couple ATP hydrolysis to local unfolding of Mad2. TRIP13 and p31 prevent APC/C inhibition by MCC components, but cannot reactivate APC/C already bound to MCC. Therefore, TRIP13-p31 intercepts and disassembles free MCC not bound to APC/C through mediating the local unfolding of the Mad2 C-terminal region.

PubMed: 29208896
DOI: 10.1038/s41467-017-02012-2

Experimental method

X-RAY DIFFRACTION (2.5 Å)