Biography
Biography: Klaus Fiedler
Abstract
The modeled Golgi dynamics domain of CHOp24, a member of intra-Golgi cargo receptors, scores highly with a collagen-binding domain and carbohydrate-binding modules and is shown to interact with Wnt8 (wingless 8) with a ï„G=-18.3 kcal/mol. Hybrid N-glycans may provide increasing energy of binding up to -7.1 kcal/mol to simulated p24-Golgi dynamics domain-ligand interaction. Apical transport may require N- and O-glycans and thus the interaction may offer insight on epithelial polarity. Groups of regulated molecules in epithelial polarization may include the sorting machinery of epithelial cells, sorted ligands or both, on top of the intricate regulatory mechanisms in substrate and intercellular adhesion. In further research I have analyzed the cargo receptor VIP36 (Vesicular-integral membrane protein of 36 kDa) for carbohydrate interaction. It has been described by me as a lectin in the endoplasmic reticulum-Golgi intermediate compartment, Golgi apparatus and plasma membrane and later was found implicated in parotid gland secretion and apical transport in MDCK cells. The docking reveals top-interacting carbohydrates of the N-glycan and O-glycan class that encompass N-linked glycans of proteins of high mannose and equally complex type which likely function as sorted ligands in epithelial cells. High affinity binding of the ganglioside GM1 carbohydrate headgroup to VIP36 suggests a linkage with protein and glycosphingolipid apical transfer in epithelial cells. Thus, this fundamental approach predicts that interchangeable glycosphingolipid/protein cargo receptor interaction, which may include some p24 family members in glycan binding, may function in apical transport.