4UI0

Crystal structure of the human RGMB-BMP2 complex, crystal form 2

Summary for 4UI0

• Entry DOI: 10.2210/pdb4ui0/pdb
• Related: 4UHY 4UHZ 4UI1 4UI2
• Descriptor: BONE MORPHOGENETIC PROTEIN 2, RGM DOMAIN FAMILY MEMBER B, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (6 entities in total)
• Functional Keywords: signaling protein, repulsive guidance molecule, bone morphogenetic protein pathway, hemojuvelin, morphogen, axon guidance, cell surface receptor signaling
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P12643; Cell membrane ; Lipid-anchor, GPI-anchor : Q6NW40
• Total number of polymer chains: 3
• Total formula weight: 36723.14

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: 2024-10-23)

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

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: 25938661
DOI: 10.1038/NSMB.3016

Experimental method

X-RAY DIFFRACTION (2.8 Å)