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6sf3
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6sf3 is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Bone morphogenetic protein 10 (BMP10) in complex with extracellular domain of activin receptor-like kinase 1 (ALK1) at 2.3 Angstrom== | |
| + | <StructureSection load='6sf3' size='340' side='right'caption='[[6sf3]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6sf3]] 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=6SF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SF3 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]] 2.3000066Å</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=6sf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sf3 OCA], [https://pdbe.org/6sf3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sf3 RCSB], [https://www.ebi.ac.uk/pdbsum/6sf3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sf3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ACVL1_HUMAN ACVL1_HUMAN] Defects in ACVRL1 are the cause of hereditary hemorrhagic telangiectasia type 2 (HHT2) [MIM:[https://omim.org/entry/600376 600376]; also known as Osler-Rendu-Weber syndrome 2 (ORW2). HHT2 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary, cerebral and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia.<ref>PMID:9245985</ref> <ref>PMID:8640225</ref> <ref>PMID:10694922</ref> <ref>PMID:10767348</ref> <ref>PMID:11170071</ref> <ref>PMID:11484689</ref> <ref>PMID:14684682</ref> <ref>PMID:15024723</ref> <ref>PMID:15712270</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ACVL1_HUMAN ACVL1_HUMAN] Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.<ref>PMID:22799562</ref> <ref>PMID:22718755</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Activin receptor-like kinase 1 (ALK1)-mediated endothelial cell signalling in response to bone morphogenetic protein 9 (BMP9) and BMP10 is of significant importance in cardiovascular disease and cancer. However, detailed molecular mechanisms of ALK1-mediated signalling remain unclear. Here, we report crystal structures of the BMP10:ALK1 complex at 2.3 A and the prodomain-bound BMP9:ALK1 complex at 3.3 A. Structural analyses reveal a tripartite recognition mechanism that defines BMP9 and BMP10 specificity for ALK1, and predict that crossveinless 2 is not an inhibitor of BMP9, which is confirmed by experimental evidence. Introduction of BMP10-specific residues into BMP9 yields BMP10-like ligands with diminished signalling activity in C2C12 cells, validating the tripartite mechanism. The loss of osteogenic signalling in C2C12 does not translate into non-osteogenic activity in vivo and BMP10 also induces bone-formation. Collectively, these data provide insight into ALK1-mediated BMP9 and BMP10 signalling, facilitating therapeutic targeting of this important pathway. | ||
| - | + | Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms.,Salmon RM, Guo J, Wood JH, Tong Z, Beech JS, Lawera A, Yu M, Grainger DJ, Reckless J, Morrell NW, Li W Nat Commun. 2020 Apr 1;11(1):1621. doi: 10.1038/s41467-020-15425-3. PMID:32238803<ref>PMID:32238803</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6sf3" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Bone morphogenetic protein 3D structures|Bone morphogenetic protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Guo J]] | ||
| + | [[Category: Li W]] | ||
| + | [[Category: Yu M]] | ||
Current revision
Bone morphogenetic protein 10 (BMP10) in complex with extracellular domain of activin receptor-like kinase 1 (ALK1) at 2.3 Angstrom
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Categories: Homo sapiens | Large Structures | Guo J | Li W | Yu M
