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| | ==Crystal structure of the human RGMA-BMP2 complex== | | ==Crystal structure of the human RGMA-BMP2 complex== |
| - | <StructureSection load='4uhy' size='340' side='right' caption='[[4uhy]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4uhy' size='340' side='right'caption='[[4uhy]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uhy]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UHY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UHY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uhy]] is a 3 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=4UHY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UHY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uhz|4uhz]], [[4ui0|4ui0]], [[4ui1|4ui1]], [[4ui2|4ui2]]</td></tr> | + | </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=4uhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uhy OCA], [https://pdbe.org/4uhy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uhy RCSB], [https://www.ebi.ac.uk/pdbsum/4uhy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uhy ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uhy OCA], [http://pdbe.org/4uhy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uhy RCSB], [http://www.ebi.ac.uk/pdbsum/4uhy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uhy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BMP2_HUMAN BMP2_HUMAN]] Induces cartilage and bone formation. [[http://www.uniprot.org/uniprot/RGMA_HUMAN RGMA_HUMAN]] Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.<ref>PMID:19273616</ref> <ref>PMID:19458235</ref> | + | [https://www.uniprot.org/uniprot/BMP2_HUMAN BMP2_HUMAN] Induces cartilage and bone formation. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Bone morphogenetic protein|Bone morphogenetic protein]] | + | *[[Bone morphogenetic protein 3D structures|Bone morphogenetic protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bell, C H]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bishop, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Elegheert, J]] | + | [[Category: Bell CH]] |
| - | [[Category: Healey, E G]] | + | [[Category: Bishop B]] |
| - | [[Category: Padilla-Parra, S]] | + | [[Category: Elegheert J]] |
| - | [[Category: Siebold, C]] | + | [[Category: Healey EG]] |
| - | [[Category: Axon guidance]] | + | [[Category: Padilla-Parra S]] |
| - | [[Category: Bone morphogenetic protein pathway]] | + | [[Category: Siebold C]] |
| - | [[Category: Cell surface receptor signaling]]
| + | |
| - | [[Category: Hemojuvelin]]
| + | |
| - | [[Category: Morphogen]]
| + | |
| - | [[Category: Signaling protein]]
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| Structural highlights
Function
BMP2_HUMAN Induces cartilage and bone formation.
Publication Abstract from PubMed
Repulsive guidance molecules (RGMs) control crucial processes including cell motility, adhesion, immune-cell regulation and systemic iron metabolism. RGMs signal via the neogenin (NEO1) and the bone morphogenetic protein (BMP) pathways. Here, we report crystal structures of the N-terminal domains of all human RGM family members in complex with the BMP ligand BMP2, revealing a new protein fold and a conserved BMP-binding mode. Our structural and functional data suggest a pH-linked mechanism for RGM-activated BMP signaling and offer a rationale for RGM mutations causing juvenile hemochromatosis. We also determined the crystal structure of the ternary BMP2-RGM-NEO1 complex, which, along with solution scattering and live-cell super-resolution fluorescence microscopy, indicates BMP-induced clustering of the RGM-NEO1 complex. Our results show how RGM acts as the central hub that links BMP and NEO1 and physically connects these fundamental signaling pathways.
Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.,Healey EG, Bishop B, Elegheert J, Bell CH, Padilla-Parra S, Siebold C Nat Struct Mol Biol. 2015 May 4. doi: 10.1038/nsmb.3016. PMID:25938661[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Healey EG, Bishop B, Elegheert J, Bell CH, Padilla-Parra S, Siebold C. Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein. Nat Struct Mol Biol. 2015 May 4. doi: 10.1038/nsmb.3016. PMID:25938661 doi:http://dx.doi.org/10.1038/nsmb.3016
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