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| - | [[Image:2qcq.jpg|left|200px]] | |
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| - | <!--
| + | ==Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)== |
| - | The line below this paragraph, containing "STRUCTURE_2qcq", creates the "Structure Box" on the page.
| + | <StructureSection load='2qcq' size='340' side='right'caption='[[2qcq]], [[Resolution|resolution]] 2.21Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <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> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21Å</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> |
| - | {{STRUCTURE_2qcq| PDB=2qcq | SCENE= }}
| + | </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]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == 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. |
| | | | |
| - | '''Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)'''
| + | 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> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | 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.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 2QCQ is a [[Single protein]] structure of sequence from [http://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].
| + | </div> |
| | + | <div class="pdbe-citations 2qcq" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17924656 17924656]
| + | *[[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: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Allendorph, G P.]] | + | [[Category: Allendorph GP]] |
| - | [[Category: Bmp]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Tgf-beta]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:44:19 2008''
| + | |
| Structural highlights
Function
BMP3_HUMAN Negatively regulates bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentitation and ossification.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Daluiski A, Engstrand T, Bahamonde ME, Gamer LW, Agius E, Stevenson SL, Cox K, Rosen V, Lyons KM. Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet. 2001 Jan;27(1):84-8. PMID:11138004 doi:http://dx.doi.org/10.1038/83810
- ↑ Kang Q, Sun MH, Cheng H, Peng Y, Montag AG, Deyrup AT, Jiang W, Luu HH, Luo J, Szatkowski JP, Vanichakarn P, Park JY, Li Y, Haydon RC, He TC. Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Ther. 2004 Sep;11(17):1312-20. PMID:15269709 doi:http://dx.doi.org/10.1038/sj.gt.3302298
- ↑ Allendorph GP, Isaacs MJ, Kawakami Y, Belmonte JC, Choe S. BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors. Biochemistry. 2007 Oct 30;46(43):12238-47. Epub 2007 Oct 9. PMID:17924656 doi:http://dx.doi.org/10.1021/bi700907k
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