View source for 4fao


==Specificity and Structure of a high affinity Activin-like 1 (ALK1) signaling complex==
<StructureSection load='4fao' size='340' side='right'caption='[[4fao]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4fao]] is a 36 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=4FAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FAO 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]] 3.357&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <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=4fao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fao OCA], [https://pdbe.org/4fao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fao RCSB], [https://www.ebi.ac.uk/pdbsum/4fao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fao ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GDF2_HUMAN GDF2_HUMAN] Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks.<ref>PMID:18309101</ref> <ref>PMID:22799562</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activin receptor-like kinase 1 (ALK1), an endothelial cell specific type I receptor of the TGF-beta superfamily, is an important regulator of normal blood vessel development as well as pathological tumor angiogenesis. As such, ALK1 is an important therapeutic target. Thus, several ALK1 directed agents are currently in clinical trials as anti-angiogenic cancer therapeutics. Given the biological and clinical importance of the ALK1 signaling pathway, we sought to elucidate the biophysical and structural basis underlying ALK1 signaling. The TGF-beta family ligands BMP9 and BMP10 as well as the three type II TGF-beta family receptors ActRIIA, ActRIIB and BMPRII have been implicated in ALK1 signaling. Here, we provide a kinetic and thermodynamic analysis of BMP9 and BMP10 interactions with ALK1 and type II receptors. Our data show that BMP9 displays a significant discrimination in type II receptor binding, while BMP10 does not. We also report the crystal structure of a fully assembled ternary complex of BMP9 with the extracellular domains of ALK1 and ActRIIB. The structure reveals that the high specificity of ALK1 for BMP9/10 is determined by a novel orientation of ALK1 with respect to BMP9, which leads to a unique set of receptor-ligand interactions. In addition, the structure explains how BMP9 discriminates between low and high affinity type II receptors. Taken together, our findings provide structural and mechanistic insights into ALK1 signaling that could serve as a basis for novel anti-angiogenic therapies.

Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex.,Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, Ucran JA, Liharska K, Underwood KW, Seehra J, Kumar R, Grinberg AV J Biol Chem. 2012 Jun 20. PMID:22718755<ref>PMID:22718755</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4fao" 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: Greppi C]]
[[Category: Grinberg AV]]
[[Category: Kumar R]]
[[Category: Liharska K]]
[[Category: Liu J]]
[[Category: Lowden P]]
[[Category: Martinez-Hackert E]]
[[Category: Sako D]]
[[Category: Seehra J]]
[[Category: Townson SA]]
[[Category: Ucran JA]]
[[Category: Underwood KW]]