View source for 6lth


==Structure of human BAF Base module==
<SX load='6lth' size='340' side='right' viewer='molstar' caption='[[6lth]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lth]] is a 8 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=6LTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LTH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6lth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lth OCA], [https://pdbe.org/6lth PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lth RCSB], [https://www.ebi.ac.uk/pdbsum/6lth PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lth ProSAT]</span></td></tr>
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== Disease ==
[https://www.uniprot.org/uniprot/SMCA4_HUMAN SMCA4_HUMAN] Defects in SMARCA4 are the cause of rhabdoid tumor predisposition syndrome type 2 (RTPS2) [MIM:[https://omim.org/entry/613325 613325]. RTPS2 is a familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood.<ref>PMID:20137775</ref>   Defects in SMARCA4 are the cause of mental retardation autosomal dominant type 16 (MRD16) [MIM:[https://omim.org/entry/614609 614609]. A disease characterized by multiple congenital anomalies and mental retardation. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. MRD16 patients manifest developmental delay, absent or hypoplastic fifth fingernails or toenails, thick eyebrows and long eyelashes, hirsutism. Additional findings include hypotonia, microcephaly, seizures, a Dandy-Walker malformation, and vision and hearing problems.<ref>PMID:22426308</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SMCA4_HUMAN SMCA4_HUMAN] Transcriptional coactivator cooperating with nuclear hormone receptors to potentiate transcriptional activation. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP. 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. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). 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. Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1.<ref>PMID:12837248</ref> <ref>PMID:19571879</ref> <ref>PMID:20418909</ref> 
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== Publication Abstract from PubMed ==
Mammalian SWI/SNF family chromatin remodelers, BRG1/BRM-associated factor (BAF) and polybromo-associated BAF (PBAF), regulate chromatin structure and transcription, and their mutations are linked to cancers. The 3.7-angstrom-resolution cryo-electron microscopy structure of human BAF bound to the nucleosome reveals that the nucleosome is sandwiched by the base and the adenosine triphosphatase (ATPase) modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, engages with and pumps DNA along the nucleosome. The C-terminal alpha helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of the nucleosome. AT-rich interactive domain-containing protein 1A (ARID1A) and the SWI/SNF complex subunit SMARCC serve as a structural core and scaffold in the base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex.

Structure of nucleosome-bound human BAF complex.,He S, Wu Z, Tian Y, Yu Z, Yu J, Wang X, Li J, Liu B, Xu Y Science. 2020 Feb 21;367(6480):875-881. doi: 10.1126/science.aaz9761. Epub 2020, Jan 30. PMID:32001526<ref>PMID:32001526</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6lth" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone 3D structures|Histone 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: He S]]
[[Category: Li J]]
[[Category: Liu B]]
[[Category: Tian Y]]
[[Category: Wang X]]
[[Category: Wu Z]]
[[Category: Xu Y]]
[[Category: Yu J]]
[[Category: Yu Z]]