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Diversity of oligomerization in Drosophila semaphorins suggests a mechanism of functional fine-tuning

DOI: 10.1038/s41467-019-11683-y DOI Help

Authors: Daniel Rozbesky (Wellcome Centre for Human Genetics, University of Oxford) , Ross A. Robinson (Wellcome Centre for Human Genetics, University of Oxford; Immunocore Ltd) , Vitul Jain (Wellcome Centre for Human Genetics, University of Oxford) , Max Renner (Wellcome Trust Centre for Human Genetics, University of Oxford) , Tomas Malinauskas (University of Wellcome Centre for Human Genetics, University of Oxford) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Christian Siebold (Wellcome Trust Centre for Human Genetics, University of Oxford) , E. Yvonne Jones (Wellcome Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 10

State: Published (Approved)
Published: August 2019
Diamond Proposal Number(s): 14744 , 10627

Open Access Open Access

Abstract: Semaphorin ligands and their plexin receptors are one of the major cell guidance factors that trigger localised changes in the cytoskeleton. Binding of semaphorin homodimer to plexin brings two plexins in close proximity which is a prerequisite for plexin signalling. This model appears to be too simplistic to explain the complexity and functional versatility of these molecules. Here, we determine crystal structures for all members of Drosophila class 1 and 2 semaphorins. Unlike previously reported semaphorin structures, Sema1a, Sema2a and Sema2b show stabilisation of sema domain dimer formation via a disulfide bond. Unexpectedly, our structural and biophysical data show Sema1b is a monomer suggesting that semaphorin function may not be restricted to dimers. We demonstrate that semaphorins can form heterodimers with members of the same semaphorin class. This heterodimerization provides a potential mechanism for cross-talk between different plexins and co-receptors to allow fine-tuning of cell signalling.

Journal Keywords: Biophysical chemistry; Extracellular signalling molecules; Molecular neuroscience; X-ray crystallography

Subject Areas: Biology and Bio-materials


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

Other Facilities: ESRF

Documents:
s41467-019-11683-y.pdf