Molecular basis of C-mannosylation - a structural perspective

Samuel Crine, R Acharya

Research output: Contribution to journalReview articlepeer-review


The structural and functional diversity of proteins can be enhanced by numerous post-translational modifications. C-mannosylation is a rare form of glycosylation consisting of a single alpha or beta D-mannopyranose forming a carbon–carbon bond with the pyrrole ring of a tryptophan residue. Despite first being discovered in 1994, C-mannosylation is still poorly understood and 3D structures are available for only a fraction of the total predicted C-mannosylated proteins. Here, we present the first comprehensive review of C-mannosylated protein structures by analysing the data for all 10 proteins with C-mannosylation/s deposited in the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). We analysed in detail the WXXW/WXXWXXW consensus motif and the highly conserved pair of arginine residues in thrombospondin type 1 repeat C-mannosylation sites or homologous arginine residues in other domains. Furthermore, we identified a conserved PXP sequence C-terminal of the C-mannosylation site. The PXP motif forms a tight turn region in the polypeptide chain and its universal conservation in C-mannosylated protein is worthy of further experimental study. The stabilization of C-mannopyranosyl groups was demonstrated through hydrogen bonding with arginine and other charged or polar amino acids. Where possible, the structural findings were linked to other functional studies demonstrating the role of C-mannosylation in protein stability, secretion or function. With the current technological advances in structural biology, we hope to see more progress in the study of C-mannosylation that may correspond to discoveries of novel C-mannosylation pathways and functions with implications for human health and biotechnology.

Original languageEnglish
JournalFEBS Journal
Early online date6 Nov 2021
Publication statusE-pub ahead of print - 6 Nov 2021


  • C-mannosylation
  • glycosylation
  • protein data bank
  • protein structure
  • structural biology
  • thrombospondin type 1 repeat

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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