View source for 2qcq


==Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)==
<StructureSection load='2qcq' size='340' side='right'caption='[[2qcq]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qcq]] is a 2 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=2QCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QCQ 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]] 2.21&#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=2qcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qcq OCA], [https://pdbe.org/2qcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qcq RCSB], [https://www.ebi.ac.uk/pdbsum/2qcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qcq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BMP3_HUMAN BMP3_HUMAN] Negatively regulates bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentitation and ossification.<ref>PMID:11138004</ref> <ref>PMID:15269709</ref> 
== 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/qc/2qcq_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=2qcq ConSurf].
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== Publication Abstract from PubMed ==
Bone morphogenetic proteins (BMPs) are extracellular messenger ligands involved in controlling a wide array of developmental and intercellular signaling processes. To initiate their specific intracellular signaling pathways, the ligands recognize and bind two structurally related serine/threonine kinase receptors, termed type I and type II, on the cell surface. Here, we present the crystal structures of BMP-3 and BMP-6, of which BMP-3 has remained poorly understood with respect to its receptor identity, affinity, and specificity. Using surface plasmon resonance (BIAcore) we show that BMP-3 binds Activin Receptor type II (ActRII) with Kd approximately 1.8 microM but ActRIIb with 30-fold higher affinity at Kd approximately 53 nM. This low affinity for ActRII may involve Ser-28 and Asp-33 of BMP-3, which are found only in BMP-3's type II receptor-binding interfaces. Point mutations of either residue to alanine results in up to 20-fold higher affinity to either receptor. We further demonstrate by Smad-based whole cell luciferase assays that the increased affinity of BMP-3S28A to ActRII enables the ligand's signaling ability to a level comparable to that of BMP-6. Focusing on BMP-3's preference for ActRIIb, we find that Lys-76 of ActRII and the structurally equivalent Glu-76 of ActRIIb are distinct between the two receptors. We demonstrate that ActRIIbE76K and ActRII bind BMP-3 with similar affinity, indicating BMP-3 receptor specificity is controlled by the interaction of Lys-30 of BMP-3 with Glu-76 of ActRIIb. These studies illustrate how a single amino acid can regulate the specificity of ligand-receptor binding and potentially alter biological signaling and function in vivo.

BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors.,Allendorph GP, Isaacs MJ, Kawakami Y, Belmonte JC, Choe S Biochemistry. 2007 Oct 30;46(43):12238-47. Epub 2007 Oct 9. PMID:17924656<ref>PMID:17924656</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2qcq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bone morphogenetic protein 3D structures|Bone morphogenetic protein 3D structures]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allendorph GP]]