Drosophila OTK is a glycosaminoglycan-binding protein with high conformational flexibility

DOI: 10.1016/j.str.2020.02.008

Authors: Daniel Rozbesky (Wellcome Centre for Human Genetics, University of Oxford) , Jim Monistrol (Wellcome Centre for Human Genetics, University of Oxford) , Vitul Jain (Wellcome Centre for Human Genetics, University of Oxford) , James Hillier (Wellcome Centre for Human Genetics, University of Oxford) , Sergi Padilla-Parra (Wellcome Centre for Human Genetics, University of Oxford; King's College London) , E. Yvonne Jones (Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure

State: Published (Approved)
Published: March 2020
Diamond Proposal Number(s): 14744

Abstract: The transmembrane protein OTK plays an essential role in plexin and Wnt signaling during Drosophila development. We have determined a crystal structure of the last three domains of the OTK ectodomain and found that OTK shows high conformational flexibility resulting from mobility at the interdomain interfaces. We failed to detect direct binding between Drosophila Plexin A (PlexA) and OTK, which was suggested previously. We found that, instead of PlexA, OTK directly binds semaphorin 1a. Our binding analyses further revealed that glycosaminoglycans, heparin and heparan sulfate, are ligands for OTK and thus may play a role in the Sema1a-PlexA axon guidance system.

Journal Keywords: OTK; Off-track; plexin; Wnt; GAG; glycosaminoglycans; Ig-like domain; signaling; PlexA; Sema1a

Subject Areas: Biology and Bio-materials


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

Added On: 25/03/2020 09:19

Documents:
PIIS0969212620300721.pdf

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)