1m4u

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(New page: 200px<br /> <applet load="1m4u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m4u, resolution 2.42&Aring;" /> '''Crystal structure o...)
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[[Image:1m4u.gif|left|200px]]<br />
 
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<applet load="1m4u" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1m4u, resolution 2.42&Aring;" />
 
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'''Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin'''<br />
 
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==Overview==
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==Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin==
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The interplay between bone morphogenetic proteins (BMPs) and their, antagonists governs developmental and cellular processes as diverse as, establishment of the embryonic dorsal-ventral axis, induction of neural, tissue, formation of joints in the skeletal system and neurogenesis in the, adult brain. So far, the three-dimensional structures of BMP antagonists, and the structural basis for inactivation have remained unknown. Here we, report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular, interfaces of the binding epitopes for both type I and type II receptors., The BMP-7-binding affinity of site-specific variants of Noggin is, correlated with alterations in bone formation and apoptosis in chick limb, development, showing that Noggin functions by sequestering its ligand in, an inactive complex. The scaffold of Noggin contains a cystine (the, oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have evolved from a common ancestral gene.
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<StructureSection load='1m4u' size='340' side='right'caption='[[1m4u]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1m4u]] 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=1M4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M4U FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4u OCA], [https://pdbe.org/1m4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m4u RCSB], [https://www.ebi.ac.uk/pdbsum/1m4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4u ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BMP7_HUMAN BMP7_HUMAN] Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m4/1m4u_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1m4u ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The interplay between bone morphogenetic proteins (BMPs) and their antagonists governs developmental and cellular processes as diverse as establishment of the embryonic dorsal-ventral axis, induction of neural tissue, formation of joints in the skeletal system and neurogenesis in the adult brain. So far, the three-dimensional structures of BMP antagonists and the structural basis for inactivation have remained unknown. Here we report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. The BMP-7-binding affinity of site-specific variants of Noggin is correlated with alterations in bone formation and apoptosis in chick limb development, showing that Noggin functions by sequestering its ligand in an inactive complex. The scaffold of Noggin contains a cystine (the oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have evolved from a common ancestral gene.
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==Disease==
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Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.,Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S Nature. 2002 Dec 12;420(6916):636-42. PMID:12478285<ref>PMID:12478285</ref>
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Known diseases associated with this structure: Stapes ankylosis syndrome without symphalangism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602991 602991]], Symphalangism, proximal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602991 602991]], Synostoses syndrome, multiple, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602991 602991]], Tarsal-carpal coalition syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602991 602991]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1M4U is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1M4U OCA].
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</div>
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<div class="pdbe-citations 1m4u" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural basis of BMP signalling inhibition by the cystine knot protein Noggin., Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S, Nature. 2002 Dec 12;420(6916):636-42. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12478285 12478285]
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*[[Bone morphogenetic protein 3D structures|Bone morphogenetic protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Affolter, M.]]
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[[Category: Affolter M]]
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[[Category: Choe, S.]]
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[[Category: Choe S]]
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[[Category: Economides, A.N.]]
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[[Category: Economides AN]]
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[[Category: Greenwald, J.]]
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[[Category: Greenwald J]]
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[[Category: Groppe, J.]]
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[[Category: Groppe J]]
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[[Category: Izpisua-Belmonte, J.C.]]
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[[Category: Izpisua-Belmonte JC]]
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[[Category: Kwiatkowski, W.]]
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[[Category: Kwiatkowski W]]
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[[Category: Rodriguez-Leon, J.]]
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[[Category: Rodriguez-Leon J]]
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[[Category: Vale, W.W.]]
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[[Category: Vale WW]]
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[[Category: Wiater, E.]]
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[[Category: Wiater E]]
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[[Category: bmp antagonist]]
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[[Category: bmp-7]]
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[[Category: bone morphogenetic protein]]
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[[Category: cystine knot]]
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[[Category: noggin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:07:27 2007''
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Current revision

Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin

PDB ID 1m4u

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