Structural highlights
Disease[RGMC_HUMAN] Hemochromatosis type 2. The disease is caused by mutations affecting the gene represented in this entry. Function[BMP2_HUMAN] Induces cartilage and bone formation. [RGMC_HUMAN] Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis.[UniProtKB:Q7TQ32] Publication Abstract from PubMedRepulsive 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 AlsoReferences
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