Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The cell-to-cell signalling mechanisms of multi-cellular organisms orchestrate human development during embryogenesis and control homeostasis in adult tissues. These are mechanisms vital to human health and perturbation of cell-to-cell signalling is a contributing factor in many pathologies including cancer. The semaphorin cell guidance cues and their cognate plexin receptors exemplify a cell-to-cell signalling system for which insights into mechanistic principles are emerging. X-ray crystallographic data from Diamond beam lines have enabled us to probe the inner workings of semaphorin-plexin signalling to atomic-level resolutions. Importantly, we can complement protein crystallographic results with biophysical and cellular studies to dovetail structural information with functional impact. The signature seven-bladed β propeller 'sema' domain of the semaphorins forms a dimer; in contrast the equivalent domain in the plexins is monomeric. The generic architecture of a semaphorin-plexin complex is characterized by the dimeric semaphorin cross-linking two copies of the plexin receptor. For specific family members, the co-receptor neuropilin serves to bolster this architecture, but in all cases, the dimeric interaction lies at the core of the ligand receptor complex, providing the essential trigger for signalling.

Original publication

DOI

10.1098/rsta.2013.0155

Type

Journal article

Journal

Philos Trans A Math Phys Eng Sci

Publication Date

06/03/2015

Volume

373

Keywords

cell guidance cue, ligand–receptor complex, neuropilin, plexin, semaphorin, Animals, Cell Adhesion Molecules, Cell Communication, Crystallography, X-Ray, Glycoproteins, Humans, Ligands, Nerve Tissue Proteins, Neuropilins, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Semaphorins, Signal Transduction