4pjw | pdb_00004pjw
crystal structure of human Stromal Antigen 2 (SA2) in complex with Sister Chromatid Cohesion protein 1 (Scc1), with bound MES
Structural highlights
FunctionSTAG2_HUMAN Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis.[1] Publication Abstract from PubMedOrderly termination of sister-chromatid cohesion during mitosis is critical for accurate chromosome segregation. During prophase, mitotic kinases phosphorylate cohesin and its protector sororin, triggering Wapl-dependent cohesin release from chromosome arms. The shugoshin (Sgo1)-PP2A complex protects centromeric cohesin until its cleavage by separase at anaphase onset. Here, we report the crystal structure of a human cohesin subcomplex comprising SA2 and Scc1. Multiple HEAT repeats of SA2 form a dragon-shaped structure. Scc1 makes extensive contacts with SA2, with one binding hotspot. Sgo1 and Wapl compete for binding to a conserved site on SA2-Scc1. At this site, mutations of SA2 residues that disrupt Wapl binding bypass the Sgo1 requirement in cohesion protection. Thus, in addition to recruiting PP2A to dephosphorylate cohesin and sororin, Sgo1 physically shields cohesin from Wapl. This unexpected, direct antagonism between Sgo1 and Wapl augments centromeric cohesion protection. Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion.,Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H Nat Struct Mol Biol. 2014 Aug 31. doi: 10.1038/nsmb.2880. PMID:25173175[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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