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4pk7

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Revision as of 08:13, 22 October 2014

crystal structure of human Stromal Antigen 2 (SA2) in complex with Sister Chromatid Cohesion protein 1 (Scc1) with bound MES, native proteins

Structural highlights

4pk7 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[RAD21_HUMAN] Cornelia de Lange syndrome. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

[STAG2_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.^[2] [RAD21_HUMAN] Cleavable component of the cohesin complex, involved in chromosome cohesion during cell cycle, in DNA repair, and in apoptosis. The cohesin complex is 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 metaphase-anaphase transition, this protein is cleaved by separase/ESPL1 and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Also plays a role in apoptosis, via its cleavage by caspase-3/CASP3 or caspase-7/CASP7 during early steps of apoptosis: the C-terminal 64 kDa cleavage product may act as a nuclear signal to initiate cytoplasmic events involved in the apoptotic pathway.^[3] ^[4]

Publication Abstract from PubMed

Orderly 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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Deardorff MA, Wilde JJ, Albrecht M, Dickinson E, Tennstedt S, Braunholz D, Monnich M, Yan Y, Xu W, Gil-Rodriguez MC, Clark D, Hakonarson H, Halbach S, Michelis LD, Rampuria A, Rossier E, Spranger S, Van Maldergem L, Lynch SA, Gillessen-Kaesbach G, Ludecke HJ, Ramsay RG, McKay MJ, Krantz ID, Xu H, Horsfield JA, Kaiser FJ. RAD21 mutations cause a human cohesinopathy. Am J Hum Genet. 2012 Jun 8;90(6):1014-27. doi: 10.1016/j.ajhg.2012.04.019. Epub, 2012 May 24. PMID:22633399 doi:http://dx.doi.org/10.1016/j.ajhg.2012.04.019
↑ Prieto I, Pezzi N, Buesa JM, Kremer L, Barthelemy I, Carreiro C, Roncal F, Martinez A, Gomez L, Fernandez R, Martinez-A C, Barbero JL. STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis. EMBO Rep. 2002 Jun;3(6):543-50. Epub 2002 May 24. PMID:12034751 doi:http://dx.doi.org/10.1093/embo-reports/kvf108
↑ Pati D, Zhang N, Plon SE. Linking sister chromatid cohesion and apoptosis: role of Rad21. Mol Cell Biol. 2002 Dec;22(23):8267-77. PMID:12417729
↑ Chen F, Kamradt M, Mulcahy M, Byun Y, Xu H, McKay MJ, Cryns VL. Caspase proteolysis of the cohesin component RAD21 promotes apoptosis. J Biol Chem. 2002 May 10;277(19):16775-81. Epub 2002 Mar 1. PMID:11875078 doi:http://dx.doi.org/10.1074/jbc.M201322200
↑ Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H. Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion. Nat Struct Mol Biol. 2014 Aug 31. doi: 10.1038/nsmb.2880. PMID:25173175 doi:http://dx.doi.org/10.1038/nsmb.2880

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4pk7"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4pk7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PK7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PK7 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pk7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pk7 RCSB], [http://www.ebi.ac.uk/pdbsum/4pk7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pk7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pk7 RCSB], [http://www.ebi.ac.uk/pdbsum/4pk7 PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/RAD21_HUMAN RAD21_HUMAN]] Cornelia de Lange syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:22633399</ref>

4pk7

From Proteopedia

Revision as of 08:13, 22 October 2014

crystal structure of human Stromal Antigen 2 (SA2) in complex with Sister Chromatid Cohesion protein 1 (Scc1) with bound MES, native proteins

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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