PXD020992

PXD020992 is an original dataset announced via ProteomeXchange.

Title	A structural model of the human mSWI/SNF (BAF) complex bound to the nucleosome informs disease mechanisms
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:18:44.068.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jie Luo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-18 23:24:23	ID requested
1	2021-02-09 23:11:51	announced
⏵ 2	2024-10-22 05:18:44	announced	2024-10-22: Updated project metadata.

Mashtalir N, Suzuki H, Farrell DP, Sankar A, Luo J, Filipovski M, D'Avino AR, St Pierre R, Valencia AM, Onikubo T, Roeder RG, Han Y, He Y, Ranish JA, DiMaio F, Walz T, Kadoch C, A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms. Cell, 183(3):802-817.e24(2020) [pubmed]

10.1016/j.cell.2020.09.051;

submitter keyword: homology model, cryo-EM, ATP-dependent chromatin remodeling, nucleosome acidic patch, yeast SWI/SNF,Mammalian SWI/SNF, canonical BAF complex, human disease, mutations

Jeff Ranish
contact affiliation	Institute For Systems Biology
contact email	jranish@systemsbiology.org
lab head
Jie Luo
contact affiliation	Institute for Systems Biology
contact email	jluo@systemsbiology.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/02/PXD020992

PRIDE project URI

• PRIDE
  1. PXD020992
     1. Label: PRIDE project
     2. Name: A structural model of the human mSWI/SNF (BAF) complex bound to the nucleosome informs disease mechanisms