7xc5
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal structure of the ANK domain of CLPB== |
| + | <StructureSection load='7xc5' size='340' side='right'caption='[[7xc5]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7xc5]] is a 1 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=7XC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XC5 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]] 2.1Å</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=7xc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xc5 OCA], [https://pdbe.org/7xc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xc5 RCSB], [https://www.ebi.ac.uk/pdbsum/7xc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xc5 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CLPB_HUMAN CLPB_HUMAN] Autosomal dominant severe congenital neutropenia;3-methylglutaconic aciduria type 7. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CLPB_HUMAN CLPB_HUMAN] Functions as a regulatory ATPase and participates in secretion/protein trafficking process. Has ATP-dependent protein disaggregase activity and is required to maintain the solubility of key mitochondrial proteins (PubMed:32573439, PubMed:34115842, PubMed:35247700, PubMed:36170828, PubMed:36745679). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117). Plays a role in granulocyte differentiation (PubMed:34115842).<ref>PMID:31522117</ref> <ref>PMID:32573439</ref> <ref>PMID:34115842</ref> <ref>PMID:35247700</ref> <ref>PMID:36170828</ref> <ref>PMID:36745679</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The human AAA+ ATPase CLPB (SKD3) is a protein disaggregase in the mitochondrial intermembrane space (IMS) and functions to promote the solubilization of various mitochondrial proteins. Loss-of-function CLPB mutations are associated with a few human diseases with neutropenia and neurological disorders. Unlike canonical AAA+ proteins, CLPB contains a unique ankyrin repeat domain (ANK) at its N-terminus. How CLPB functions as a disaggregase and the role of its ANK domain are currently unclear. Herein, we report a comprehensive structural characterization of human CLPB in both the apo- and substrate-bound states. CLPB assembles into homo-tetradecamers in apo-state and is remodeled into homo-dodecamers upon substrate binding. Conserved pore-loops (PLs) on the ATPase domains form a spiral staircase to grip and translocate the substrate in a step-size of 2 amino acid residues. The ANK domain is not only responsible for maintaining the higher-order assembly but also essential for the disaggregase activity. Interactome analysis suggests that the ANK domain may directly interact with a variety of mitochondrial substrates. These results reveal unique properties of CLPB as a general disaggregase in mitochondria and highlight its potential as a target for the treatment of various mitochondria-related diseases. | ||
| - | + | Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization.,Wu D, Liu Y, Dai Y, Wang G, Lu G, Chen Y, Li N, Lin J, Gao N PLoS Biol. 2023 Feb 6;21(2):e3001987. doi: 10.1371/journal.pbio.3001987. , eCollection 2023 Feb. PMID:36745679<ref>PMID:36745679</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7xc5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gao N]] | ||
| + | [[Category: Lin J]] | ||
| + | [[Category: Liu Y]] | ||
| + | [[Category: Lu G]] | ||
| + | [[Category: Wu D]] | ||
Current revision
Crystal structure of the ANK domain of CLPB
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Categories: Homo sapiens | Large Structures | Gao N | Lin J | Liu Y | Lu G | Wu D
