C-mannosylation and O-fucosylation of the thrombospondin type 1 module

Citation
J. Hofsteenge et al., C-mannosylation and O-fucosylation of the thrombospondin type 1 module, J BIOL CHEM, 276(9), 2001, pp. 6485-6498
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
9
Year of publication
2001
Pages
6485 - 6498
Database
ISI
SICI code
0021-9258(20010302)276:9<6485:CAOOTT>2.0.ZU;2-S
Abstract
Thrombospondin-1 (TSP-1) is a multidomain protein that has been implicated in cell adhesion, motility, and growth. Some of these functions have been l ocalized to the three thrombospondin type 1 repeats (TSRs), modules of simi lar to 60 amino acids in length with conserved Cys and Trp residues. The Tr p residues occur in WXXW patterns, which are the recognition motifs for pro tein C-mannosylation. This modification involves the attachment of an cu-ma nnosyl residue to the C-2 atom of the first tryptophan. Analysis of human p latelet TSP-1 revealed that Trp-368, -420, -423, and -480 are C-mannosylate d. Mannosylation also occurred in recombinant, baculovirally expressed TSR modules from Sf9 and "High Five" cells, contradictory to earlier reports th at such cells do not carry out this reaction. In the course of these studie s it was appreciated that the TSRs in TSP-1 undergo a second form of unusua l glycosylation. By using a novel mass spectrometric approach, it was found that Ser-377, Thr-432, and Thr-489 in the motif CSX(S/T)CG carry the O-Lin ked disaccharide Glc-Fuc-O-Ser-Thr. This is the first protein in which such a disaccharide has been identified, although protein O-fucosylation is wel l described in epidermal growth factor-like modules. Both C- and O-glycosyl ations take place on residues that have been implicated in the interaction of TSP-1 with glycosaminoglycans or other cellular receptors.