| First Author | Healey EG | Year | 2015 |
| Journal | Nat Struct Mol Biol | Volume | 22 |
| Issue | 6 | Pages | 458-65 |
| PubMed ID | 25938661 | Mgi Jnum | J:245275 |
| Mgi Id | MGI:5915531 | Doi | 10.1038/nsmb.3016 |
| Citation | Healey EG, et al. (2015) Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein. Nat Struct Mol Biol 22(6):458-65 |
| abstractText | 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. |
