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.
Keywords:
GAG; Ig-like domain; OTK; Off-track; PlexA; Sema1a; Wnt; glycosaminoglycans; plexin; signaling.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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COS Cells
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Cell Membrane / metabolism
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Chlorocebus aethiops
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Cricetulus
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Crystallography, X-Ray
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Drosophila Proteins / chemistry*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Fluorescence Resonance Energy Transfer
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Glycosaminoglycans / metabolism
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HEK293 Cells
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Heparin / metabolism
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Heparitin Sulfate / metabolism
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Humans
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Nerve Tissue Proteins / metabolism
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Protein Conformation
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Protein Domains
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Protein Interaction Maps
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Receptor Protein-Tyrosine Kinases / chemistry*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Cell Surface / metabolism
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Semaphorins / metabolism
Substances
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Drosophila Proteins
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Glycosaminoglycans
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Nerve Tissue Proteins
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Receptors, Cell Surface
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Semaphorins
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plexA protein, Drosophila
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semaphorin 1a, Drosophila
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Heparin
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Heparitin Sulfate
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Otk protein, Drosophila
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Receptor Protein-Tyrosine Kinases