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Synovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes

Nat Struct Mol Biol .. 2024-01;

Zebin 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

Products/Services Used	Details	Operation
Proteins, Expression, Isolation and Analysis	o express the GST-tagged SSX1 and its mutants, DNA sequences coding human SSX1(111–188) or its mutants with codon optimization in Escherichia coli species were synthesized and cloned into the pGEX-6P-2 vector /Gene sequences (after codon optimization) of wild-type Ub and its mutants (UbG76C) were cloned into pET22b(+) vectors (GenScript). (GenScript)/Peak fractions were resolved on 8–16% SurePAGE Bis-Tris (GenScript) gels	Get A Quote
Gene Synthesis		Get A Quote

摘要

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 ... More