6sf2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "6sf2" [edit=sysop:move=sysop])
Current revision (12:41, 24 January 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6sf2 is ON HOLD
+
==Ternary complex of human bone morphogenetic protein 9 (BMP9) growth factor domain, its prodomain and extracellular domain of activin receptor-like kinase 1 (ALK1).==
 +
<StructureSection load='6sf2' size='340' side='right'caption='[[6sf2]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6sf2]] is a 6 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=6SF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SF2 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]] 3.3&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6sf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sf2 OCA], [https://pdbe.org/6sf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sf2 RCSB], [https://www.ebi.ac.uk/pdbsum/6sf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sf2 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.
-
Authors:
+
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>
-
Description:
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
 +
<div class="pdbe-citations 6sf2" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[Growth differentiation factor 3D STRUCTURES|Growth differentiation factor 3D STRUCTURES]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Guo J]]
 +
[[Category: Li W]]
 +
[[Category: Salmon RM]]
 +
[[Category: Yu M]]

Current revision

Ternary complex of human bone morphogenetic protein 9 (BMP9) growth factor domain, its prodomain and extracellular domain of activin receptor-like kinase 1 (ALK1).

PDB ID 6sf2

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6sf2"
Personal tools