6UCH

SMARCB1 nucleosome-interacting C-terminal alpha helix

Summary for 6UCH

• Entry DOI: 10.2210/pdb6uch/pdb
• NMR Information: BMRB: 30672
• Descriptor: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (1 entity in total)
• Functional Keywords: mswi-snf complex, baf complex, chromatin remodeling, smarcb1, baf47, positive charge cluster, arginine cluster, nucleosome binding, alpha helix, nuclear protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 4748.47

Authors

Valencia, A.M.,Sun, Z.Y.J.,Seo, H.S.,Vangos, H.S.,Yeoh, Z.C.,Mashtalir, N.,Dhe-Paganon, S.,Kadoch, C. (deposition date: 2019-09-16, release date: 2019-11-27, Last modification date: 2024-05-01)

Primary citation

Valencia, A.M.,Collings, C.K.,Dao, H.T.,St Pierre, R.,Cheng, Y.C.,Huang, J.,Sun, Z.Y.,Seo, H.S.,Mashtalir, N.,Comstock, D.E.,Bolonduro, O.,Vangos, N.E.,Yeoh, Z.C.,Dornon, M.K.,Hermawan, C.,Barrett, L.,Dhe-Paganon, S.,Woolf, C.J.,Muir, T.W.,Kadoch, C.
Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling.
Cell, 179:1342-1356.e23, 2019

PubMed Abstract: Mammalian switch/sucrose non-fermentable (mSWI/SNF) complexes are multi-component machines that remodel chromatin architecture. Dissection of the subunit- and domain-specific contributions to complex activities is needed to advance mechanistic understanding. Here, we examine the molecular, structural, and genome-wide regulatory consequences of recurrent, single-residue mutations in the putative coiled-coil C-terminal domain (CTD) of the SMARCB1 (BAF47) subunit, which cause the intellectual disability disorder Coffin-Siris syndrome (CSS), and are recurrently found in cancers. We find that the SMARCB1 CTD contains a basic α helix that binds directly to the nucleosome acidic patch and that all CSS-associated mutations disrupt this binding. Furthermore, these mutations abrogate mSWI/SNF-mediated nucleosome remodeling activity and enhancer DNA accessibility without changes in genome-wide complex localization. Finally, heterozygous CSS-associated SMARCB1 mutations result in dominant gene regulatory and morphologic changes during iPSC-neuronal differentiation. These studies unmask an evolutionarily conserved structural role for the SMARCB1 CTD that is perturbed in human disease.

PubMed: 31759698
DOI: 10.1016/j.cell.2019.10.044

Experimental method

SOLUTION NMR