5wc2 | pdb_00005wc2
Crystal Structure of ADP-bound human TRIP13
Structural highlights
Function[PCH2_HUMAN] Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (By similarity). Publication Abstract from PubMedThe 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(comet) and the ATPase TRIP13 promote MCC disassembly and checkpoint silencing. Here, using nuclear magnetic resonance (NMR) spectroscopy, we show that TRIP13 and p31(comet) 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(comet)-Mad2 binding and couple ATP hydrolysis to local unfolding of Mad2. TRIP13 and p31(comet) prevent APC/C inhibition by MCC components, but cannot reactivate APC/C already bound to MCC. Therefore, TRIP13-p31(comet) intercepts and disassembles free MCC not bound to APC/C through mediating the local unfolding of the Mad2 C-terminal region. Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing.,Brulotte ML, Jeong BC, Li F, Li B, Yu EB, Wu Q, Brautigam CA, Yu H, Luo X Nat Commun. 2017 Dec 5;8(1):1956. doi: 10.1038/s41467-017-02012-2. PMID:29208896[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
