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 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.
Highlights
p24s are usually described as type I transmembrane proteins containing a GOLD domain
p24-GOLD can be modeled based on the Sec14-like protein with X-ray structure quality
A concave patch on the p24 surface binds to diverse ligands
N-glycans may provide increased binding energy in p24-cargo interaction
Wnt binding to TMED2 may quench signaling similar to a decoy-type mechanism
- Abbreviations
- APC
- adenomatous polyposis coli
- CBM
- carbohydrate binding module
- CHO
- chinese hamster ovary (from Cricetulus griseus)
- Dpp
- decapentaplegic
- EMT
- epithelial-mesenchymal transition
- ER
- endoplasmic reticulum
- Evi
- evenness interrupted
- FRT
- Fischer rat thyroid
- Fz8
- frizzled-8
- GalNAc
- N-acetylgalactosamine
- GlcNAc
- N-acetylglucosamine
- GlcNAcT-I
- GlcNAc-Transferase I
- GOLD
- Golgi-dynamics
- Golgi-Man
- Golgi-mannosidase
- GPI-anchor
- glycosylphosphatidylinositol-anchor
- GRASP
- Golgi reassembly and stacking protein
- GSL
- glycosphingolipid
- LEF
- lymphoid enhancer binding factor
- Man
- mannose
- MDCK
- Madin-Darby Canine Kidney
- MINOS
- myo-inositol
- NeuAc
- N-acetylneuraminic acid
- PIG-A
- PI (phosphatidylinositol) GlcNAcT gene
- Rets
- regulator of exopolysaccharide and type III secretion
- TCF
- T-cell transcription factor
- TGF
- transforming growth factor
- TMED
- transmembrane emp24 domain containing
- TLR4
- toll-like receptor 4
- VIP36
- vesicular-integral membrane protein of 36 kD
- Wnt
- wingless
