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Overview

C-Mannosylation is a unique type of protein glycosylation. A C-C bond is formed between the C1 atom of an α-mannose and the C2 atom of the indole ring of a tryptophan residue via mannosyl-transferases.

In-depth mechanism

Glycosylations of proteins are one of the most common and widespread post-translational modifications. Best known are N– and O-glycosylations. More than 25 years ago, a new type of glycosylation, C-mannosylation, was discovered. C-Mannosylation differs fundamentally from previously described types of glycosylation. A C-C bond is formed between the C1 atom of an α-mannose and the C2 atom of the indole ring of a tryptophan residue. The reaction is catalysed by mannosyltransferases, which use dolychyl-phosphate-mannose as donor for the mannose moiety^​1,2​. Dolychyl-phosphate-mannose is formed from GDP-mannose and dolichol-phosphate on the cytosolic side of the endoplasmatic reticulum^​3​. The mechanism of C-mannosylation is shownin figure 1.

Mannosyltransferases recognize W-X-X-W motifs and C-mannosylate the first tryptophan in the sequence. However, this pattern can vary slightly from organism to organism^​2​. The exchange of the second tryptophan residue for other amino acids strongly restricts or even completely prevents C-mannosylation. The influence of the two amino acids between the tryptophan residues is still the subject of current studies^​1​. The W-X-X-W motif occurs in many proteins, which suggests that C-mannosylation is a common an widespread post-translational modification. The function of C-mannosylation is still largely unknown today^​1,2​. The hydrophobicity of a protein is not altered by C-mannosylation.