Proteomics

Dataset Information

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A structural model of the human mSWI/SNF (BAF) complex bound to the nucleosome informs disease mechanisms


ABSTRACT: Mammalian SWI/SNF complexes are multi-component ATP-dependent chromatin-remodeling complexes that regulate genomic architecture. Here we present the first structural model of the human canonical BAF chromatin-remodeling complex bound to a nucleosome generated using cryo-EM, cross-linking mass spectrometry, and homology modeling. Endogenously-purified BAF tethers to the nucleosome H2A/H2B acidic patch regions bilaterally through the SMARCB1 C-terminal helix and a SMARCA4 C-terminal post-SnAc region, each of which are mutated in disease and disrupt nucleosome remodeling. We describe the structural organization of the BAF core module, a connecting ARP module and the ATPase module, scaffolded by the SMARCA4/2 ATPase subunits. Importantly, we assign and model disease-associated mutations throughout the entire BAF complex, identifying mutations that break identified subunit–nucleosome contacts and subunit–subunit interfaces of BAF in the nucleosome-bound conformation. Taken together, this comprehensive structural model of the human BAF complex provides the first insights into the functional impact of mutations that cause cancer and other diseases.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jie Luo  

LAB HEAD: Jeff Ranish

PROVIDER: PXD020992 | Pride | 2021-02-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
BAF-NCP.inter1.xls Xls
BAF-NCP.intra1.xls Xls
JL021919_030919_BAF_NCP_sp3.mzXML Mzxml
JL021919_030919_BAF_NCP_sp3_100B.mzXML Mzxml
JL021919_030919_BAF_NCP_sp3_30B.mzXML Mzxml
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Publications


Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture. Here, we present a structural model of the endogenously purified human canonical BAF complex bound to the nucleosome, generated using cryoelectron microscopy (cryo-EM), cross-linking mass spectrometry, and homology modeling. BAF complexes bilaterally engage the nucleosome H2A/H2B acidic patch regions through the SMARCB1 C-terminal α-helix and the SMARCA4/2 C-terminal SnAc/post-SnAc re  ...[more]

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