The Wnt segment polarity pathway and TMED2 protein may interact via a lectin- and decoy-type mechanism

Abstract

AbstractThe Secl4-like protein (280-385 GOLD-domain) in this study scores highly with the carbohydrate-binding module (CBM) of the RetS domain from Pseudomonas aeruginosa. The thereupon modeled Cricetulus griseus p24-GOLD domain of p24, a member of intra-Golgi cargo receptors, is shown to interact with Wnt8 (wingless 8) of Xenopus laevis with a ΔG=-18.3 kcal/mol. Lower ranked models listed a smaller ΔG (PDBePISA) and energy of Del Phi interaction. Complex/hybrid N-glycans provide increasing energy of binding up to −7.1 kcal/mol to simulated p24-GOLD-ligand interaction. It is likely, that Wnt proteins and p24 cargo-receptors interact analogously to Wnt-Frizzled and that Wnt transport may involve early lectin binding. The possibly promiscuous interaction of p24-GOLD with ligands, including collagen, may shed light on cargo-receptor mediated traffic.Highlightsp24s are usually described as type I transmembrane proteins containing a GOLD domainp24-GOLD can be modeled based on the Sec14-like protein with X-ray structure qualityA concave patch on the p24 surface binds to diverse ligandsN-glycans may provide increased binding energy in p24-cargo interactionWnt binding to TMED2 may quench signaling similar to a decoy-type mechanism