EMD-34954

Single-particle
3.05 Å
EMD-34954 Deposition: 14/12/2022
Map released: 27/09/2023
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-34954

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

EMD-34954

Single-particle
3.05 Å
EMD-34954 Deposition: 14/12/2022
Map released: 27/09/2023
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: SSX1-H2AK119Ub nucleosome complex
Fitted models: 8hqy (Avg. Q-score: 0.47)

Deposition Authors: Zebin T, Ai HS, Ziyu X, GuoChao C, Man P, Liu L
Synovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes.
Tong Z , Ai H , Xu Z, He K , Chu GC, Shi Q, Deng Z , Xue Q, Sun M , Du Y , Liang L, Li JB, Pan M , Liu L
(2024) Nat Struct Mol Biol , 31 , 300 - 310
PUBMED: 38177667
DOI: doi:10.1038/s41594-023-01141-1
ISSN: 1545-9985
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.