Publication

Article Metrics

Citations


Online attention

Structural basis of semaphorin‐plexin cis interaction

DOI: 10.15252/embj.2019102926 DOI Help

Authors: Daniel Rozbesky (Wellcome Centre for Human Genetics, University of Oxford) , Marieke G. Verhagen (University Medical Center Utrecht, Utrecht University) , Dimple Karia (Wellcome Centre for Human Genetics, University of Oxford) , Gergely N. Nagy (Wellcome Centre for Human Genetics, University of Oxford) , Luis Alvarez (Wellcome Centre for Human Genetics, University of Oxford) , Ross A Robinson (Wellcome Centre for Human Genetics, University of Oxford) , Karl Harlos (Wellcome Centre for Human Genetics, University of Oxford) , Sergi Padilla‐parra (Wellcome Centre for Human Genetics, University of Oxford) , R. Jeroen Pasterkamp (University Medical Center Utrecht, Utrecht University) , Edith Y. Jones (Wellcome Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal , VOL 58

State: Published (Approved)
Published: June 2020
Diamond Proposal Number(s): 10627

Open Access Open Access

Abstract: Semaphorin ligands interact with plexin receptors to contribute to functions in the development of myriad tissues including neurite guidance and synaptic organisation within the nervous system. Cell‐attached semaphorins interact in trans with plexins on opposing cells, but also in cis on the same cell. The interplay between trans and cis interactions is crucial for the regulated development of complex neural circuitry, but the underlying molecular mechanisms are uncharacterised. We have discovered a distinct mode of interaction through which the Drosophila semaphorin Sema1b and mouse Sema6A mediate binding in cis to their cognate plexin receptors. Our high‐resolution structural, biophysical and in vitro analyses demonstrate that monomeric semaphorins can mediate a distinctive plexin binding mode. These findings suggest the interplay between monomeric vs dimeric states has a hereto unappreciated role in semaphorin biology, providing a mechanism by which Sema6s may balance cis and trans functionalities.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Documents:
embj.2019102926.pdf