Structural highlights
Function
[NEO1_MOUSE] May be involved as a regulatory protein in the transition of undifferentiated proliferating cells to their differentiated state. May also function as a cell adhesion molecule in a broad spectrum of embryonic and adult tissues. [RGMB_HUMAN] Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system (By similarity). Acts as a bone morphogenetic protein (BMP) coreceptor that potentiates BMP signaling (By similarity). Promotes neuronal adhesion (By similarity). May inhibit neurite outgrowth.
Publication Abstract from PubMed
Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes including motility and adhesion, immune cell regulation and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called Dragon). The RGMB structure reveals a novel protein fold, a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors, in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways.
Structure of the Repulsive Guidance Molecule (RGM)-Neogenin Signaling Hub.,Bell CH, Healey E, van Erp S, Bishop B, Tang C, Gilbert RJ, Aricescu AR, Pasterkamp RJ, Siebold C Science. 2013 Jun 6. PMID:23744777[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bell CH, Healey E, van Erp S, Bishop B, Tang C, Gilbert RJ, Aricescu AR, Pasterkamp RJ, Siebold C. Structure of the Repulsive Guidance Molecule (RGM)-Neogenin Signaling Hub. Science. 2013 Jun 6. PMID:23744777 doi:10.1126/science.1232322
