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| | <StructureSection load='6yxp' size='340' side='right'caption='[[6yxp]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6yxp' size='340' side='right'caption='[[6yxp]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6yxp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YXP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yxp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YXP FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMARCC1, BAF155 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6yxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yxp OCA], [https://pdbe.org/6yxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yxp RCSB], [https://www.ebi.ac.uk/pdbsum/6yxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yxp ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6yxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yxp OCA], [https://pdbe.org/6yxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yxp RCSB], [https://www.ebi.ac.uk/pdbsum/6yxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yxp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SMRC1_HUMAN SMRC1_HUMAN]] Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). May stimulate the ATPase activity of the catalytic subunit of the complex. Also involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity).<ref>PMID:12837248</ref> <ref>PMID:11018012</ref>
| + | [https://www.uniprot.org/uniprot/SMRC1_HUMAN SMRC1_HUMAN] Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). May stimulate the ATPase activity of the catalytic subunit of the complex. Also involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity).<ref>PMID:12837248</ref> <ref>PMID:11018012</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allen, M D]] | + | [[Category: Allen MD]] |
| - | [[Category: Bycroft, M]] | + | [[Category: Bycroft M]] |
| - | [[Category: Zinzalla, G]] | + | [[Category: Zinzalla G]] |
| - | [[Category: Baf155]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Swi/snf-subunit]]
| + | |
| Structural highlights
Function
SMRC1_HUMAN Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). May stimulate the ATPase activity of the catalytic subunit of the complex. Also involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity).[1] [2]
Publication Abstract from PubMed
SWI/SNF (BAF) chromatin remodelling complexes are key regulators of gene expression programs, and attractive drug targets for cancer therapies. Here we show that the N-terminus of the BAF155/SMARCC1 subunit contains a putative DNA-binding MarR-like domain, a chromodomain and a BRCT domain that are interconnected to each other to form a distinct module. In this structure the chromodomain makes interdomain interactions and has lost its canonical function to bind to methylated lysines. The structure provides new insights into the missense mutations that target this module in cancer. This study also reveals two adjacent, highly-conserved pockets in a cleft between the domains that form a potential binding site, which can be targeted with small molecules, offering a new strategy to target SWI/SNF complexes.
SWI/SNF subunit BAF155 N-terminus structure informs the impact of cancer-associated mutations and reveals a potential drug binding site.,Allen MD, Freund SMV, Bycroft M, Zinzalla G Commun Biol. 2021 May 5;4(1):528. doi: 10.1038/s42003-021-02050-z. PMID:33953332[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003 Jun 27;113(7):905-17. PMID:12837248
- ↑ Kadam S, McAlpine GS, Phelan ML, Kingston RE, Jones KA, Emerson BM. Functional selectivity of recombinant mammalian SWI/SNF subunits. Genes Dev. 2000 Oct 1;14(19):2441-51. PMID:11018012
- ↑ Allen MD, Freund SMV, Bycroft M, Zinzalla G. SWI/SNF subunit BAF155 N-terminus structure informs the impact of cancer-associated mutations and reveals a potential drug binding site. Commun Biol. 2021 May 5;4(1):528. doi: 10.1038/s42003-021-02050-z. PMID:33953332 doi:http://dx.doi.org/10.1038/s42003-021-02050-z
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