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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RGMB_HUMAN RGMB_HUMAN]] Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system (By similarity). Acts as a bone morphogenetic protein (BMP) coreceptor that potentiates BMP signaling (By similarity). Promotes neuronal adhesion (By similarity). May inhibit neurite outgrowth. [[http://www.uniprot.org/uniprot/NEO1_MOUSE NEO1_MOUSE]] May be involved as a regulatory protein in the transition of undifferentiated proliferating cells to their differentiated state. May also function as a cell adhesion molecule in a broad spectrum of embryonic and adult tissues. [[http://www.uniprot.org/uniprot/BMP2_HUMAN BMP2_HUMAN]] Induces cartilage and bone formation.
[[http://www.uniprot.org/uniprot/RGMB_HUMAN RGMB_HUMAN]] Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system (By similarity). Acts as a bone morphogenetic protein (BMP) coreceptor that potentiates BMP signaling (By similarity). Promotes neuronal adhesion (By similarity). May inhibit neurite outgrowth. [[http://www.uniprot.org/uniprot/NEO1_MOUSE NEO1_MOUSE]] May be involved as a regulatory protein in the transition of undifferentiated proliferating cells to their differentiated state. May also function as a cell adhesion molecule in a broad spectrum of embryonic and adult tissues. [[http://www.uniprot.org/uniprot/BMP2_HUMAN BMP2_HUMAN]] Induces cartilage and bone formation.
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== Publication Abstract from PubMed ==
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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.
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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<ref>PMID:25938661</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
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<references/>
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Revision as of 06:30, 20 May 2015

Crystal structure of the ternary RGMB-BMP2-NEO1 complex

4ui2, resolution 3.15Å

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