4UI2
Crystal structure of the ternary RGMB-BMP2-NEO1 complex
Summary for 4UI2
| Entry DOI | 10.2210/pdb4ui2/pdb |
| Related | 4UHY 4UHZ 4UI0 4UI1 |
| Descriptor | NEOGENIN, BONE MORPHOGENETIC PROTEIN 2, BMP2, REPULSIVE GUIDANCE MOLECULE C, RGMC, HEMOJUVELIN, ... (7 entities in total) |
| Functional Keywords | repulsive guidance molecule, bone morphogenetic protein pathway, hemojuvelin, morphogen, axon guidance, cell surface receptor signaling, neogenin, signaling protein |
| Biological source | HOMO SAPIENS (HUMAN) More |
| Total number of polymer chains | 4 |
| Total formula weight | 84505.59 |
| Authors | Healey, E.G.,Bishop, B.,Elegheert, J.,Bell, C.H.,Padilla-Parra, S.,Siebold, C. (deposition date: 2015-03-27, release date: 2015-05-06, Last modification date: 2020-07-29) |
| Primary citation | Healey, E.G.,Bishop, B.,Elegheert, J.,Bell, C.H.,Padilla-Parra, S.,Siebold, C. Repulsive Guidance Molecule is a Structural Bridge between Neogenin and Bone Morphogenetic Protein. Nat.Struct.Mol.Biol., 22:458-, 2015 Cited by PubMed Abstract: 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. PubMed: 25938661DOI: 10.1038/NSMB.3016 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.15 Å) |
Structure validation
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