8R8B
Wnt binding to COPalpha and COPBeta2 directs secretion on extracellular vesicles
This is a non-PDB format compatible entry.
Summary for 8R8B
| Entry DOI | 10.2210/pdb8r8b/pdb |
| Descriptor | Coatomer subunit beta', Small ribosomal subunit protein mS37, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | wnt signalling, coatomer complex, wnt7a, regenerative myogenesis, copi vesicles, copalpha, copbeta2, extracellular vesicles, exosomes, signal peptide., transport protein |
| Biological source | Saccharomyces cerevisiae (brewer's yeast) More |
| Total number of polymer chains | 48 |
| Total formula weight | 874180.85 |
| Authors | Gurriaran-Rodriguez, U.,Datzkiw, D.,Radusky, L.G.,Fisher, F.,Xiao, F.,Ming, H.,De Repentigny, Y.,Kothary, R.,Serrano, L.,Rojas, A.L.,Hierro, A.,Rudnicki, M.A. (deposition date: 2023-11-28, release date: 2024-11-13, Last modification date: 2024-12-25) |
| Primary citation | Gurriaran-Rodriguez, U.,Datzkiw, D.,Radusky, L.G.,Esper, M.,Javandoost, E.,Xiao, F.,Ming, H.,Fisher, S.,Marina, A.,De Repentigny, Y.,Kothary, R.,Azkargorta, M.,Elortza, F.,Rojas, A.L.,Serrano, L.,Hierro, A.,Rudnicki, M.A. Identification of the Wnt signal peptide that directs secretion on extracellular vesicles. Sci Adv, 10:eado5914-eado5914, 2024 Cited by PubMed Abstract: Wnt proteins are hydrophobic glycoproteins that are nevertheless capable of long-range signaling. We found that Wnt7a is secreted long distance on the surface of extracellular vesicles (EVs) following muscle injury. We defined a signal peptide region in Wnts required for secretion on EVs, termed exosome-binding peptide (EBP). Addition of EBP to an unrelated protein directed secretion on EVs. Palmitoylation and the signal peptide were not required for Wnt7a-EV secretion. Coatomer was identified as the EV-binding protein for the EBP. Analysis of cocrystal structures, binding thermodynamics, and mutagenesis found that a dilysine motif mediates EBP binding to coatomer with a conserved function across the Wnt family. We showed that EBP is required for Wnt7a bioactivity when expressed in vivo during regeneration. Overall, our study has elucidated the structural basis and singularity of Wnt secretion on EVs, alternatively to canonical secretion, opening avenues for innovative therapeutic targeting strategies and systemic protein delivery. PubMed: 39661666DOI: 10.1126/sciadv.ado5914 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.808 Å) |
Structure validation
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