3fby
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The crystal structure of the signature domain of cartilage oligomeric matrix protein.== |
| + | <StructureSection load='3fby' size='340' side='right'caption='[[3fby]], [[Resolution|resolution]] 3.15Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3fby]] is a 3 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=3FBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FBY 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]] 3.15Å</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>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3fby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fby OCA], [https://pdbe.org/3fby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fby RCSB], [https://www.ebi.ac.uk/pdbsum/3fby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fby ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/COMP_HUMAN COMP_HUMAN] Defects in COMP are the cause of multiple epiphyseal dysplasia type 1 (EDM1) [MIM:[https://omim.org/entry/132400 132400]. EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types.<ref>PMID:11084047</ref> <ref>PMID:7670472</ref> <ref>PMID:9021009</ref> <ref>PMID:9184241</ref> <ref>PMID:9463320</ref> <ref>PMID:9921895</ref> <ref>PMID:9452026</ref> <ref>PMID:11565064</ref> <ref>PMID:21922596</ref> Defects in COMP are the cause of pseudoachondroplasia (PSACH) [MIM:[https://omim.org/entry/177170 177170]. PSAC is a dominantly inherited chondrodysplasia characterized by short stature and early-onset osteoarthrosis. PSACH is more severe than EDM1 and is recognized in early childhood.<ref>PMID:10852928</ref> <ref>PMID:11084047</ref> <ref>PMID:7670472</ref> <ref>PMID:9184241</ref> <ref>PMID:9463320</ref> <ref>PMID:9921895</ref> <ref>PMID:9452026</ref> <ref>PMID:21922596</ref> <ref>PMID:7670471</ref> <ref>PMID:9452063</ref> <ref>PMID:11746045</ref> <ref>PMID:11746044</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/COMP_HUMAN COMP_HUMAN] May play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin. Can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors. Could play a role in the pathogenesis of osteoarthritis. Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins (BIRC3, BIRC2, BIRC5 and XIAP). Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli. Maintains this phenotype of VSMCs by interacting with ITGA7 (By similarity).<ref>PMID:16051604</ref> <ref>PMID:16542502</ref> <ref>PMID:17993464</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fb/3fby_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fby ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cartilage oligomeric matrix protein (COMP), or thrombospondin-5 (TSP-5), is a secreted glycoprotein that is important for growth plate organization and function. Mutations in COMP cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1). In this study, we determined the structure of a recombinant protein that contains the last epidermal growth factor repeat, the type 3 repeats and the C-terminal domain (CTD) of COMP to 3.15-A resolution limit by X-ray crystallography. The CTD is a beta-sandwich that is composed of 15 antiparallel beta-strands, and the type 3 repeats are a contiguous series of calcium binding sites that associate with the CTD at multiple points. The crystal packing reveals an exposed potential metal-ion-dependent adhesion site (MIDAS) on one edge of the beta-sandwich that is common to all TSPs and may serve as a binding site for collagens and other ligands. Disease-causing mutations in COMP disrupt calcium binding, disulfide bond formation, intramolecular interactions, or sites for potential ligand binding. The structure presented here and its unique molecular packing in the crystal identify potential interactive sites for glycosaminoglycans, integrins, and collagens, which are key to cartilage structure and function. | ||
| - | + | The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding.,Tan K, Duquette M, Joachimiak A, Lawler J FASEB J. 2009 Aug;23(8):2490-501. Epub 2009 Mar 10. PMID:19276170<ref>PMID:19276170</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3fby" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lawler J]] | ||
| + | [[Category: Tan K]] | ||
Current revision
The crystal structure of the signature domain of cartilage oligomeric matrix protein.
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