7ME4
Structure of the extracellular WNT-binding module in Drosophila Ror2/Nrk
Summary for 7ME4
| Entry DOI | 10.2210/pdb7me4/pdb |
| Descriptor | 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) |
| Functional Keywords | wnt signaling, receptor tyrosine kinases, acylation, growth factor signaling, co-receptor, pseudokinases, ligand, receptor, cancer, signaling protein |
| Biological source | Drosophila melanogaster (Fruit fly) |
| Total number of polymer chains | 1 |
| Total formula weight | 33266.45 |
| Authors | Mendrola, J.M.,Shi, F.,Perry, K.,Stayrook, S.E.,Lemmon, M.A. (deposition date: 2021-04-06, release date: 2021-10-13, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 34686333DOI: 10.1016/j.celrep.2021.109834 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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