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TitleSynovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes.
Journal, issue, pagesNat Struct Mol Biol, Vol. 31, Issue 2, Page 300-310, Year 2024
Publish dateJan 4, 2024
AuthorsZebin Tong / Huasong Ai / Ziyu Xu / Kezhang He / Guo-Chao Chu / Qiang Shi / Zhiheng Deng / Qiaomei Xue / Maoshen Sun / Yunxiang Du / Lujun Liang / Jia-Bin Li / Man Pan / Lei Liu /
PubMed AbstractThe 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 ...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.
External linksNat Struct Mol Biol / PubMed:38177667
MethodsEM (single particle)
Resolution3.02 - 6.11 Å
Structure data

34954

8hqy

EMDB-34954, PDB-8hqy:
Cryo-EM structure of SSX1 bound to the H2AK119Ub nucleosome at a resolution of 3.05 angstrom
Method: EM (single particle) / Resolution: 3.05 Å

34956

8hr1

EMDB-34956, PDB-8hr1:
Cryo-EM structure of SSX1 bound to the unmodified nucleosome at a resolution of 3.02 angstrom
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-34957: Cryo-EM structure of H2AK119Ub nucleosome at a resolution of 6.11 angstrom
Method: EM (single particle) / Resolution: 6.11 Å

EMDB-36747: Cryo-EM structure of 2 SSX1 bound to H2AK119Ub nucleosome at a resolution of 3.6 angstroms (2:1 complex)
Method: EM (single particle) / Resolution: 3.6 Å

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / SSX1 / H2AK119Ub nucleosome / Synovial Sarcoma / ssBAF / reader protein / unmodified nucleosome

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