View source for 6rrk


==Crystal structure of the central region of human cohesin subunit STAG1 in complex with RAD21 peptide==
<StructureSection load='6rrk' size='340' side='right'caption='[[6rrk]], [[Resolution|resolution]] 3.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rrk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RRK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RRK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.17&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rrk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rrk OCA], [https://pdbe.org/6rrk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rrk RCSB], [https://www.ebi.ac.uk/pdbsum/6rrk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rrk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/STAG1_HUMAN STAG1_HUMAN] STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/STAG1_HUMAN STAG1_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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cohesin subunit STAG2 has emerged as a recurrently inactivated tumor suppressor in human cancers. Using candidate approaches, recent studies have revealed a synthetic lethal interaction between STAG2 and its paralog STAG1 To systematically probe genetic vulnerabilities in the absence of STAG2, we have performed genome-wide CRISPR screens in isogenic cell lines and identified STAG1 as the most prominent and selective dependency of STAG2-deficient cells. Using an inducible degron system, we show that chemical genetic degradation of STAG1 protein results in the loss of sister chromatid cohesion and rapid cell death in STAG2-deficient cells, while sparing STAG2-wild-type cells. Biochemical assays and X-ray crystallography identify STAG1 regions that interact with the RAD21 subunit of the cohesin complex. STAG1 mutations that abrogate this interaction selectively compromise the viability of STAG2-deficient cells. Our work highlights the degradation of STAG1 and inhibition of its interaction with RAD21 as promising therapeutic strategies. These findings lay the groundwork for the development of STAG1-directed small molecules to exploit synthetic lethality in STAG2-mutated tumors.

STAG1 vulnerabilities for exploiting cohesin synthetic lethality in STAG2-deficient cancers.,van der Lelij P, Newman JA, Lieb S, Jude J, Katis V, Hoffmann T, Hinterndorfer M, Bader G, Kraut N, Pearson MA, Peters JM, Zuber J, Gileadi O, Petronczki M Life Sci Alliance. 2020 May 28;3(7). pii: 3/7/e202000725. doi:, 10.26508/lsa.202000725. Print 2020 Jul. PMID:32467316<ref>PMID:32467316</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rrk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Edwards A]]
[[Category: Gileadi O]]
[[Category: Newman JA]]
[[Category: Katis VL]]
[[Category: Von Delft F]]