View source for 2hlq


==Crystal Structure of the Extracellular Domain of the Type II BMP Receptor==
<StructureSection load='2hlq' size='340' side='right'caption='[[2hlq]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hlq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HLQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HLQ 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]] 1.45&#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=2hlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hlq OCA], [https://pdbe.org/2hlq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hlq RCSB], [https://www.ebi.ac.uk/pdbsum/2hlq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hlq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BMPR2_HUMAN BMPR2_HUMAN] Defects in BMPR2 are the cause of primary pulmonary hypertension (PPH1) [MIM:[https://omim.org/entry/178600 178600]. PPH1 is a rare autosomal dominant disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.<ref>PMID:10903931</ref> <ref>PMID:11015450</ref> <ref>PMID:10973254</ref> <ref>PMID:11115378</ref> <ref>PMID:12358323</ref> <ref>PMID:15965979</ref>   Defects in BMPR2 are a cause of pulmonary venoocclusive disease (PVOD) [MIM:[https://omim.org/entry/265450 265450]. PVOD is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with PPH1 has been speculative. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH1.<ref>PMID:12446270</ref> <ref>PMID:16429395</ref> 
== Function ==
[https://www.uniprot.org/uniprot/BMPR2_HUMAN BMPR2_HUMAN] 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. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hl/2hlq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hlq ConSurf].
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== Publication Abstract from PubMed ==
BMPRII is a type II TGF-beta serine threonine kinase receptor which is integral to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand specificity with the activin type II receptor, ActRII. In contrast to activin and TGF-beta type ligands, BMPs bind to type II receptors with lower affinity than type I receptors. Crystals of the BMPRII ectodomain were grown in two different forms, both of which diffracted to high resolution. The tetragonal form exhibited some disorder, whereas the entire polypeptide was seen in the orthorhombic form. The two structures retain the basic three-finger toxin fold of other TGF-beta receptor ectodomains, and share the main hydrophobic patch used by ActRII to bind various ligands. However, they present different conformations of the A-loop at the periphery of the proposed ligand-binding interface, in conjunction with rearrangement of a disulfide bridge within the loop. This particular disulfide (Cys94-Cys117) is only present in BMPRII and activin receptors, suggesting that it is important for their likely shared mode of binding. Evidence is presented that the two crystal forms represent ligand-bound and free conformations of BMPRII. Comparison with the solved structure of ActRII bound to BMP2 suggests that His87, unique amongst TGF-beta receptors, may play a key role in ligand recognition.

High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: implications for ligand binding.,Mace PD, Cutfield JF, Cutfield SM Biochem Biophys Res Commun. 2006 Dec 29;351(4):831-8. Epub 2006 Nov 10. PMID:17094948<ref>PMID:17094948</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Ovis aries]]
[[Category: Cutfield JF]]
[[Category: Cutfield SM]]
[[Category: Mace PD]]