PMID: 10878002

 

    Legend: Sugar

Title : Properdin , the positive regulator of complement, is highly C-mannosylated

Abstract :
  1. Properdin is the positive regulator of the alternative pathway of complement activation
  2. The 53-kDa protein is essentially composed of six thrombospondin type 1 repeats, all of which contain the WXXW motif , the recognition sequence for C-mannosylation
  3. C-Mannosylation is a post-translational modification of tryptophan residues in which, in contrast to the well known N- and O-glycosylation, the carbohydrate is attached via a C-C bond to C-2 of the indole moiety of tryptophan
  4. C-Mannosylation was first found in human RNase 2 and interleukin-12
  5. The terminal complement proteins C6-C9 also carry this modification as part of their thrombospondin type 1 repeats
  6. We studied the C-mannosylation pattern of human properdin by mass spectrometry and Edman degradation
  7. Properdin contains 20 tryptophans of which 17 are part of a WXXW motif
  8. Fourteen tryptophans were found to be modified 100%
  9. This is the first example of a protein in which the majority of tryptophan residues occurs in the C-mannosylated form
  10. These results show that C-mannosylated proteins occur at several steps along the complement activation cascade
  11. Therefore, this system would be ideal to investigate the function of C-mannosylation