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Originally published In Press as doi:10.1074/jbc.M001732200 on June 30, 2000
J. Biol. Chem., Vol. 275, Issue 37, 28569-28574, September 15, 2000
Properdin, the Positive Regulator of Complement, Is Highly
C-Mannosylated*
Steffen
Hartmann and
Jan
Hofsteenge
From the Friedrich-Miescher Institut, CH-4058 Basel,
Switzerland
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.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Friedrich-Miescher
Institut, Maulbeerstr. 66, CH-4058 Basel, Switzerland. Tel.: 41-61-697-4531; Fax: 41-61-697-3976; E-mail:
Jan.Hofsteenge@fmi.ch.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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