8HQY

Cryo-EM structure of SSX1 bound to the H2AK119Ub nucleosome at a resolution of 3.05 angstrom

Summary for 8HQY

• Entry DOI: 10.2210/pdb8hqy/pdb
• EMDB information: 34954
• Descriptor: Histone H3, DNA (136-MER), Histone H4 (Fragment), ... (10 entities in total)
• Functional Keywords: ssx1, h2ak119ub nucleosome, synovial sarcoma, ssbaf, reader protein, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 180393.42

Authors

Zebin, T.,Ai, H.S.,Ziyu, X.,GuoChao, C.,Man, P.,Liu, L. (deposition date: 2022-12-14, release date: 2023-09-27, Last modification date: 2024-03-06)

Primary citation

Tong, Z.,Ai, H.,Xu, Z.,He, K.,Chu, G.C.,Shi, Q.,Deng, Z.,Xue, Q.,Sun, M.,Du, Y.,Liang, L.,Li, J.B.,Pan, M.,Liu, L.
Synovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes.
Nat.Struct.Mol.Biol., 31:300-310, 2024

PubMed Abstract: The cancer-specific fusion oncoprotein SS18-SSX1 disturbs chromatin accessibility by hijacking the BAF complex from the promoters and enhancers to the Polycomb-repressed chromatin regions. This process relies on the selective recognition of H2AK119Ub nucleosomes by synovial sarcoma X breakpoint 1 (SSX1). However, the mechanism underlying the selective recognition of H2AK119Ub nucleosomes by SSX1 in the absence of ubiquitin (Ub)-binding capacity remains unknown. Here we report the cryo-EM structure of SSX1 bound to H2AK119Ub nucleosomes at 3.1-Å resolution. Combined in vitro biochemical and cellular assays revealed that the Ub recognition by SSX1 is unique and depends on a cryptic basic groove formed by H3 and the Ub motif on the H2AK119 site. Moreover, this unorthodox binding mode of SSX1 induces DNA unwrapping at the entry/exit sites. Together, our results describe a unique mode of site-specific ubiquitinated nucleosome recognition that underlies the specific hijacking of the BAF complex to Polycomb regions by SS18-SSX1 in synovial sarcoma.

PubMed: 38177667
DOI: 10.1038/s41594-023-01141-1

Experimental method

ELECTRON MICROSCOPY (3.05 Å)