2lcr
From Proteopedia
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==NMR Structure of Alk1 extracellular domain== | ==NMR Structure of Alk1 extracellular domain== | ||
| - | <StructureSection load='2lcr' size='340' side='right' caption='[[2lcr | + | <StructureSection load='2lcr' size='340' side='right'caption='[[2lcr]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2lcr]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2lcr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LCR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LCR FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</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=2lcr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lcr OCA], [https://pdbe.org/2lcr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lcr RCSB], [https://www.ebi.ac.uk/pdbsum/2lcr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lcr ProSAT]</span></td></tr> | |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </table> |
| - | <table> | + | |
== Disease == | == 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 == | == 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 == | ||
| + | Bone morphogenetic proteins (BMPs) are secreted signaling proteins - they transduce their signals by assembling complexes comprised of one of three known type II receptors and one of four known type I receptors. BMP-9 binds and signals through the type I receptor Alk1, but not other Alks, while BMP-2, -4, and -7 bind and signal through Alk3, and the close homologue Alk6, but not Alk1. The present results, which include the determination of the Alk1 structure using NMR and identification of residues important for binding using SPR, show that the beta-strand framework of Alk1 is highly similar to Alk3, yet there are significant differences in loops shown previously to be important for binding. The most pronounced difference is in the N-terminal portion of the beta4-beta5 loop, which is structurally ordered and includes a similarly placed but shorter helix in Alk1 compared to Alk3. The altered conformation of the beta4-beta5 loop, and to lesser extent beta1-beta2 loop, cause clashes when Alk1 is positioned onto BMP-9 in the manner that Alk3 is positioned onto BMP-2. This necessitates an alternative manner of binding, which is supported by a model of the BMP-9/Alk1 complex constructed using the program RosettaDock. The model shows that Alk1 is positioned similar to Alk3 but is rotated by 40 deg. The alternate positioning allows Alk1 to bind BMP-9 through a large hydrophobic interface, consistent with mutational analysis that identified several residues in the central portion of the beta4-beta5 loop that contribute significantly to binding and are nonconservatively substituted relative to the corresponding residues in Alk3. | ||
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| + | Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties.,Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. PMID:22799562<ref>PMID:22799562</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2lcr" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Ilangovan | + | [[Category: Ilangovan U]] |
| - | + | ||
Current revision
NMR Structure of Alk1 extracellular domain
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