7dg5

From Proteopedia

Crystal structure of mouse Smc1-Smc3 hinge domain containing a D574Y mutation

Structural highlights

7dg5 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SMC1A_MOUSE Involved in chromosome cohesion during cell cycle and in DNA repair. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, and works as a downstream effector in the ATM/NBS1 branch of S-phase checkpoint (By similarity). Central component of cohesin complex. 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 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. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint.

Publication Abstract from PubMed

Cohesin's association with and translocation along chromosomal DNAs depend on an ATP hydrolysis cycle driving the association and subsequent release of DNA. This involves DNA being 'clamped' by Scc2 and ATP-dependent engagement of cohesin's Smc1 and Smc3 head domains. Scc2's replacement by Pds5 abrogates cohesin's ATPase and has an important role in halting DNA loop extrusion. The ATPase domains of all SMC proteins are separated from their hinge dimerisation domains by 50-nm-long coiled coils, which have been observed to zip up along their entire length and fold around an elbow, thereby greatly shortening the distance between hinges and ATPase heads. Whether folding exists in vivo or has any physiological importance is not known. We present here a cryo-EM structure of the apo form of cohesin that reveals the structure of folded and zipped-up coils in unprecedented detail and shows that Scc2 can associate with Smc1's ATPase head even when it is fully disengaged from that of Smc3. Using cysteine-specific crosslinking, we show that cohesin's coiled coils are frequently folded in vivo, including when cohesin holds sister chromatids together. Moreover, we describe a mutation (SMC1D588Y) within Smc1's hinge that alters how Scc2 and Pds5 interact with Smc1's hinge and that enables Scc2 to support loading in the absence of its normal partner Scc4. The mutant phenotype of loading without Scc4 is only explicable if loading depends on an association between Scc2/4 and cohesin's hinge, which in turn requires coiled coil folding.

Folding of cohesin's coiled coil is important for Scc2/4-induced association with chromosomes.,Petela NJ, Gonzalez Llamazares A, Dixon S, Hu B, Lee BG, Metson J, Seo H, Ferrer-Harding A, Voulgaris M, Gligoris T, Collier J, Oh BH, Lowe J, Nasmyth KA Elife. 2021 Jul 14;10:e67268. doi: 10.7554/eLife.67268. PMID:34259632^[1]

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

References

↑ Petela NJ, Gonzalez Llamazares A, Dixon S, Hu B, Lee BG, Metson J, Seo H, Ferrer-Harding A, Voulgaris M, Gligoris T, Collier J, Oh BH, Lowe J, Nasmyth KA. Folding of cohesin's coiled coil is important for Scc2/4-induced association with chromosomes. Elife. 2021 Jul 14;10:e67268. doi: 10.7554/eLife.67268. PMID:34259632 doi:http://dx.doi.org/10.7554/eLife.67268