Abstract
SummaryThe 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.
Highlights
Drosophila off-track or OTK is a transmembrane protein that plays important roles in development and reproduction
Drosophila OTK has been described as an ortholog of the vertebrate protein tyrosine kinase 7 (PTK7), which was identified as a Wnt co-receptor required for control of planar cell polarity (Lu et al, 2004)
We further discovered that OTK interacts with glycosaminoglycans, which could explain the ability of OTK to form complexes with numerous structurally divergent proteins
Summary
Drosophila off-track or OTK is a transmembrane protein that plays important roles in development and reproduction. OTK, previously called Dtrk, was initially identified as a neural cell adhesion molecule (Pulido et al, 1992). Sequence analysis suggests that OTK is a singlepass transmembrane protein with five extracellular immunoglobulin (Ig)-like domains, which show homology with neural cell adhesion molecules (Pulido et al, 1992). The intracellular domain shows homology with receptor tyrosine kinases; the kinase domain is probably not active since conserved residues implicated in autophosphorylation are altered in OTK. Drosophila OTK has been described as an ortholog of the vertebrate protein tyrosine kinase 7 (PTK7), which was identified as a Wnt co-receptor required for control of planar cell polarity (Lu et al, 2004). OTK2 comprises only three extracellular Ig-like domains and a short cytoplasmic domain (Linnemannstons et al, 2014)
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