Title : Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib
Abstract :
We report the amino acid sequence of a 299-residue segment from the alpha chain of the human platelet membrane glycoprotein Ib
This includes the complete sequence of the amino-terminal tryptic fragment of 290 residues comprising the von Willebrand factor-binding domain
Two primary sets of overlapping fragments were obtained by cleavage of the S-carboxymethylated protein at methionyl and lysyl bonds following treatment with cyanogen bromide and Achromobacter protease I , respectively
Additional fragments were obtained by treatment of native glycocalicin with trypsin , Staphylococcus aureus V8 protease , and Serratia marcescens protease
Analysis of all these fragments provided data that allowed determination of the continuous sequence corresponding to approximately half of the alpha-chain polypeptide
This region of glycoprotein Ib is largely hydrophobic and contains only two N-linked and one O-linked carbohydrate chains
A hydrophilic region exists between residues 215 and 299 , which contains a cluster of 10 negatively charged residues at 269-287
This area is likely to attract positively charged molecules
The hydrophilic, highly glycosylated (at serine and threonine residues ) region corresponding to the previously described " macroglycopeptide " and representing the carboxyl-terminal half of the alpha chain is likely to begin at residue 292
The determined sequence of the alpha chain of glycoprotein Ib contains a region ( residues 29-193 ) with seven repeats, which is indicative of gene duplication and is highly homologous to human leucine-rich alpha 2-glycoprotein
This protein sequence agrees completely with that deduced from the cDNA sequence reported by Lopez et al. [Lopez, J.A., Chung, D.W., Fujikawa, K., Hagen, F.S., Papayannopoulou, T. & Roth, G.J. ( 1987) Proc