View source for 7ppc


==Ternary signalling complex of BMP10 bound to ALK1 and BMPRII==
<StructureSection load='7ppc' size='340' side='right'caption='[[7ppc]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ppc]] is a 12 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=7PPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPC 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]] 3.6&#8491;</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=7ppc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppc OCA], [https://pdbe.org/7ppc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppc RCSB], [https://www.ebi.ac.uk/pdbsum/7ppc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppc ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Heterozygous mutations in BMPR2 (bone morphogenetic protein (BMP) receptor type II) cause pulmonary arterial hypertension. BMPRII is a receptor for over 15 BMP ligands, but why BMPR2 mutations cause lung-specific pathology is unknown. To elucidate the molecular basis of BMP:BMPRII interactions, we report crystal structures of binary and ternary BMPRII receptor complexes with BMP10, which contain an ensemble of seven different BMP10:BMPRII 1:1 complexes. BMPRII binds BMP10 at the knuckle epitope, with the A-loop and beta4 strand making BMPRII-specific interactions. The BMPRII binding surface on BMP10 is dynamic, and the affinity is weaker in the ternary complex than in the binary complex. Hydrophobic core and A-loop interactions are important in BMPRII-mediated signalling. Our data reveal how BMPRII is a low affinity receptor, implying that forming a signalling complex requires high concentrations of BMPRII, hence mutations will impact on tissues with highest BMPR2 expression such as the lung vasculature.

Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10.,Guo J, Liu B, Thorikay M, Yu M, Li X, Tong Z, Salmon RM, Read RJ, Ten Dijke P, Morrell NW, Li W Nat Commun. 2022 May 3;13(1):2395. doi: 10.1038/s41467-022-30111-2. PMID:35504921<ref>PMID:35504921</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ppc" 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: Read RJ]]
[[Category: Yu M]]