Critical role of the carbohydrate side chains of collagen in platelet aggregation.
The reaction between human platelet membrane glucosyl transferase and collagen has recently been proposed as the mechanism for pletelet-collagen adhesion. Collagen contains glucosyl-galactose and galactose side chains linked through the galactose to hydroxylysine. Oxidation of the 6-hydroxymethyl position of the galactosyl residue to aldehydes with galactose oxidase completely abolishes platelet aggregation. This enzymatic modification of collagen can be fully reversed by reduction of the aldehydes formed by NaBH(4) with complete restoration of platelet aggregating ability. Limited digestion with bacterial collagenase abolishes the ability of collagen to aggregate platelets. Removal of the N-terminal telopeptides from collagen with trypsin does not affect platelet aggregation. Tertiary structure of soluble collagen is essential for platelet aggregation. Normal collagen is less effective than lathyritic collagen, which contains only a small number of cross-links. The decreased number of aldehyde groups in the lathyritic collagen are not responsible for the increase in aggregating ability, since reduction with NaBH(4) does not alter platelet aggregation. These results suggest that integrity and accessibility of the galactose receptor site may be crucial for the formation of a ternary collagenenzyme-platelet membrane complex which must precede platelet aggregation.
D000429:Alcohol Oxidoreductases; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects; D001894:Borohydrides; D002417:Cattle; D003094:Collagen / Q000494:pharmacology*; D004589:Electrophoresis, Disc; D005690:Galactose; D006168:Guinea Pigs; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D007842:Lathyrism; D003012:Microbial Collagenase; D010084:Oxidation-Reduction; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D012867:Skin; D013329:Structure-Activity Relationship; D014357:Trypsin
D001894:Borohydrides; D003094:Collagen; D000429:Alcohol Oxidoreductases; D014357:Trypsin; D003012:Microbial Collagenase; D005690:Galactose