ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes.
Cell Rep
; 37(3): 109834, 2021 10 19.
Article
em En
| MEDLINE
| ID: mdl-34686333
ABSTRACT
WNTs play key roles in development and disease, signaling through Frizzled (FZD) seven-pass transmembrane receptors and numerous co-receptors including ROR and RYK family receptor tyrosine kinases (RTKs). We describe crystal structures and WNT-binding characteristics of extracellular regions from the Drosophila ROR and RYK orthologs Nrk (neurospecific receptor tyrosine kinase) and Derailed-2 (Drl-2), which bind WNTs though a FZD-related cysteine-rich domain (CRD) and WNT-inhibitory factor (WIF) domain respectively. Our crystal structures suggest that neither Nrk nor Drl-2 can accommodate the acyl chain typically attached to WNTs. The Nrk CRD contains a deeply buried bound fatty acid, unlikely to be exchangeable. The Drl-2 WIF domain lacks the lipid-binding site seen in WIF-1. We also find that recombinant DWnt-5 can bind Drosophila ROR and RYK orthologs despite lacking an acyl chain. Alongside analyses of WNT/receptor interaction sites, our structures provide further insight into how WNTs may recruit RTK co-receptors into signaling complexes.
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MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
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Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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Proteínas de Drosophila
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Drosophila melanogaster
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Proteínas Wnt
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Via de Sinalização Wnt
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article