Structure of the Repulsive Guidance Molecule (RGM)–Neogenin Signaling Hub

Bell CH., Healey E., van Erp S., Bishop B., Tang C., Gilbert RJC., Aricescu AR., Pasterkamp RJ., Siebold C.

RGM Proteins Members of the repulsive guidance molecule (RGM) family of proteins can be secreted or reside on the surface of cells where they bind to the cell surface receptor, neogenin. The RGM proteins are named for their role in axon guidance for developing neurons, but their function is also linked to a range of human diseases, including inflammation, multiple sclerosis, and cancer. Bell et al. (p. 77 ) solved the crystal structures of the external portions of the RGMB protein with portions of neogenin. The structures revealed interactions of dimers of RGMB with neogenin in which ligand binding induced conformational changes that may initiate intracellular signaling from the receptor. RGM proteins contain a site of autocatalytic cleavage that affects secretion of the proteins, and some disease-associated mutations in RGM proteins were clustered at this site.

DOI

10.1126/science.1232322

Type

Journal article

Journal

Science

Publisher

American Association for the Advancement of Science (AAAS)

Publication Date

05/07/2013

Volume

341

Pages

77 - 80

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