4UI1: Crystal Structure Of The Human Rgmc-bmp2 Complex

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.
PDB ID: 4UI1Download
MMDB ID: 129065
PDB Deposition Date: 2015/3/27
Updated in MMDB: 2015/06
Experimental Method:
x-ray diffraction
Resolution: 2.35  Å
Source Organism:
Similar Structures:
Biological Unit for 4UI1: dimeric; determined by author and by software (PISA)
Molecular Components in 4UI1
Label Count Molecule
Proteins (2 molecules)
Hemojuvelin(Gene symbol: HJV)
Molecule annotation
Bone Morphogenetic Protein 2(Gene symbol: BMP2)
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB