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

Abstract

The 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 {Delta}G=-18.3 kcal/mol. Lower ranked models listed a smaller {Delta}G (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.\n\nHighlightsO_LIp24s are usually described as type I transmembrane proteins containing a GOLD domain\nC_LIO_LIp24-GOLD can be modeled based on the Sec14-like protein with X-ray structure quality\nC_LIO_LIA concave patch on the p24 surface binds to diverse ligands\nC_LIO_LIN-glycans may provide increased binding energy in p24-cargo interaction\nC_LIO_LIWnt binding to TMED2 may quench signaling similar to a decoy-type mechanism\nC_LI