Title :
Properdin , the positive regulator of complement, is highly C-mannosylated
Abstract :
- Properdin is the positive regulator of the alternative pathway of complement activation
- 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
- 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
- C-Mannosylation was first found in human RNase 2 and interleukin-12
- The terminal complement proteins C6-C9 also carry this modification as part of their thrombospondin type 1 repeats
- We studied the C-mannosylation pattern of human properdin by mass spectrometry and Edman degradation
- Properdin contains 20 tryptophans of which 17 are part of a WXXW motif
- Fourteen tryptophans were found to be modified 100%
- This is the first example of a protein in which the majority of tryptophan residues occurs in the C-mannosylated form
- These results show that C-mannosylated proteins occur at several steps along the complement activation cascade
- Therefore, this system would be ideal to investigate the function of C-mannosylation