8z3f
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Complex structure of CIB2 and TMC1 CR1== | |
| + | <StructureSection load='8z3f' size='340' side='right'caption='[[8z3f]], [[Resolution|resolution]] 1.74Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8z3f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8Z3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Z3F FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=8z3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8z3f OCA], [https://pdbe.org/8z3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8z3f RCSB], [https://www.ebi.ac.uk/pdbsum/8z3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8z3f ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CIB2_MOUSE CIB2_MOUSE] Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis (PubMed:23023331, PubMed:28663585, PubMed:29084757, PubMed:29255404, PubMed:34089643). Acts as an auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells (PubMed:34089643). Essential for mechanoelectrical transduction (MET) currents in auditory hair cells and thereby required for hearing (PubMed:28663585, PubMed:29084757, PubMed:29255404). Regulates the function of hair cell mechanotransduction by controlling the distribution of transmembrane channel-like proteins TMC1 and TMC2, and by regulating the function of the MET channels in hair cells (PubMed:34089643). Required for the maintenance of auditory hair cell stereocilia bundle morphology and function and for hair-cell survival in the cochlea (PubMed:28663585, PubMed:29084757, PubMed:29255404). Critical for proper photoreceptor cell maintenance and function (PubMed:23023331). Plays a role in intracellular calcium homeostasis by decreasing ATP-induced calcium release (PubMed:23023331). Seems to be dispensable for vestibular functions (PubMed:29084757).<ref>PMID:23023331</ref> <ref>PMID:28663585</ref> <ref>PMID:29084757</ref> <ref>PMID:29255404</ref> <ref>PMID:34089643</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | TMC1, a unique causative gene associated with deafness, exhibits variants with autosomal dominant and recessive inheritance patterns. TMC1 codes for the transmembrane channel-like protein 1 (TMC1), a key component of the mechano-electrical transduction (MET) machinery for hearing. However, the molecular mechanism of Ca(2+) regulation in MET remains unclear. Calcium and integrin-binding protein 2 (CIB2), another MET component associated with deafness, can bind with Ca(2+). Our study shows that TMC1-CIB2 complex undergoes a Ca(2+)-induced conformational change. We identified a vertebrate-specific binding site on TMC1 that interacts with apo CIB2, linked with hearing loss. Using an ex vivo mouse organotypic cochlea model, we demonstrated that disruption of the calcium-binding site of CIB2 perturbs the MET channel conductivity. After systematically analyzing the hearing loss variants, we observed dominant mutations of TMC1 cluster around the putative ion pore or at the binding interfaces with CIB2. These findings elucidate the molecular mechanisms underlying TMC1-linked hearing loss. | ||
| - | + | Mechano-electrical transduction components TMC1-CIB2 undergo a Ca(2+)-induced conformational change linked to hearing loss.,Wu S, Lin L, Hu Q, Yao X, Wang H, Liu S, Liu Q, Xi Y, Lin Y, Gong J, Hu R, Zhan W, Luo Y, He G, Liu Z, Xiong W, Wang Q, Xu Z, Bai F, Lu Q Dev Cell. 2025 Jan 24:S1534-5807(25)00004-8. doi: 10.1016/j.devcel.2025.01.004. PMID:39889697<ref>PMID:39889697</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8z3f" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Lin L]] | ||
| + | [[Category: Lu Q]] | ||
| + | [[Category: Wu S]] | ||
Current revision
Complex structure of CIB2 and TMC1 CR1
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Categories: Large Structures | Mus musculus | Lin L | Lu Q | Wu S
