7ME4

Structure of the extracellular WNT-binding module in Drosophila Ror2/Nrk

7ME4 の概要

• エントリーDOI: 10.2210/pdb7me4/pdb
• 分子名称: Tyrosine-protein kinase transmembrane receptor Ror2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, PALMITOLEIC ACID, ... (4 entities in total)
• 機能のキーワード: wnt signaling, receptor tyrosine kinases, acylation, growth factor signaling, co-receptor, pseudokinases, ligand, receptor, cancer, signaling protein
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33266.45

構造登録者

Mendrola, J.M.,Shi, F.,Perry, K.,Stayrook, S.E.,Lemmon, M.A. (登録日: 2021-04-06, 公開日: 2021-10-13, 最終更新日: 2024-10-23)

主引用文献

Shi, F.,Mendrola, J.M.,Sheetz, J.B.,Wu, N.,Sommer, A.,Speer, K.F.,Noordermeer, J.N.,Kan, Z.Y.,Perry, K.,Englander, S.W.,Stayrook, S.E.,Fradkin, L.G.,Lemmon, M.A.
ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes.
Cell Rep, 37:109834-109834, 2021

PubMed 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.

PubMed: 34686333
DOI: 10.1016/j.celrep.2021.109834

実験手法

X-RAY DIFFRACTION (1.75 Å)