7VRB

Structure of the Human BRG1/SS18 complex

Summary for 7VRB

• Entry DOI: 10.2210/pdb7vrb/pdb
• Descriptor: SMARCA4 protein,Protein SSXT (2 entities in total)
• Functional Keywords: four-helix bundle, oncoprotein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 62759.44

Authors

Cheng, Y.,Chen, F.,Zhou, H.,Long, J. (deposition date: 2021-10-22, release date: 2022-05-25, Last modification date: 2024-05-29)

Primary citation

Cheng, Y.,Shen, Z.,Gao, Y.,Chen, F.,Xu, H.,Mo, Q.,Chu, X.,Peng, C.L.,McKenzie, T.T.,Palacios, B.E.,Hu, J.,Zhou, H.,Long, J.
Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas.
Nat Commun, 13:2724-2724, 2022

PubMed Abstract: Oncoprotein SS18-SSX is a hallmark of synovial sarcomas. However, as a part of the SS18-SSX fusion protein, SS18's function remains unclear. Here, we depict the structures of both human SS18/BRG1 and yeast SNF11/SNF2 subcomplexes. Both subcomplexes assemble into heterodimers that share a similar conformation, suggesting that SNF11 might be a homologue of SS18 in chromatin remodeling complexes. Importantly, our study shows that the self-association of the intrinsically disordered region, QPGY domain, leads to liquid-liquid phase separation (LLPS) of SS18 or SS18-SSX and the subsequent recruitment of BRG1 into phase-separated condensates. Moreover, our results show that the tyrosine residues in the QPGY domain play a decisive role in the LLPS of SS18 or SS18-SSX. Perturbations of either SS18-SSX LLPS or SS18-SSX's binding to BRG1 impair NIH3T3 cell transformation by SS18-SSX. Our data demonstrate that both LLPS and assembling into chromatin remodelers contribute to the oncogenic activity of SS18-SSX in synovial sarcomas.

PubMed: 35585082
DOI: 10.1038/s41467-022-30447-9

Experimental method

X-RAY DIFFRACTION (2.389 Å)