6sf3

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<StructureSection load='6sf3' size='340' side='right'caption='[[6sf3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='6sf3' size='340' side='right'caption='[[6sf3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6sf3]] is a 2 chain structure. 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 [http://proteopedia.org/fgij/fg.htm?mol=6SF3 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6sf3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6SF3 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6sf1|6sf1]]</td></tr>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6sf1|6sf1]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACVRL1, ACVRLK1, ALK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BMP10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sf3 OCA], [http://pdbe.org/6sf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sf3 RCSB], [http://www.ebi.ac.uk/pdbsum/6sf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sf3 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sf3 OCA], [http://pdbe.org/6sf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sf3 RCSB], [http://www.ebi.ac.uk/pdbsum/6sf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sf3 ProSAT]</span></td></tr>
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== Function ==
== Function ==
[[http://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> [[http://www.uniprot.org/uniprot/BMP10_HUMAN BMP10_HUMAN]] Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.<ref>PMID:16049014</ref> <ref>PMID:17068149</ref> <ref>PMID:20608934</ref>
[[http://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> [[http://www.uniprot.org/uniprot/BMP10_HUMAN BMP10_HUMAN]] Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.<ref>PMID:16049014</ref> <ref>PMID:17068149</ref> <ref>PMID:20608934</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6sf3" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Receptor protein serine/threonine kinase]]
[[Category: Receptor protein serine/threonine kinase]]

Revision as of 07:17, 15 April 2020

Bone morphogenetic protein 10 (BMP10) in complex with extracellular domain of activin receptor-like kinase 1 (ALK1) at 2.3 Angstrom

PDB ID 6sf3

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