Structural highlights
4ui2 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 4uhy, 4uhz, 4ui0, 4ui1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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. [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. [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
