Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib

K. Titani, K. Takio, M. Handa, Z. M. Ruggeri

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Abstract

We report the amino acid sequence of a 299-residue segment from the α chain of the human platelet membrane glycoprotein Ib. This includes the complete sequence of the amino-terminal cryptic 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 fllowing 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 α-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 glycosated (at serine and threonine residues) region corresponding to the previously described 'macroglycopeptide' and representing the carboxyl-terminal half of the α chain is likely to begin at residue 292. The determined sequence of the α chain of glycoprotein Ib contains a region (residues 29-193) with seven repeats, which is indication of gene duplication and is highly homologous to human leucine-rich α2-glycoprotein. This protein sequence agrees completely with that deduced from the cDNA sequence reported by Lopez et al.

Original languageEnglish
Pages (from-to)5610-5614
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number16
Publication statusPublished - 1987
Externally publishedYes

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Platelet Glycoprotein GPIb-IX Complex
lysyl endopeptidase
von Willebrand Factor
Amino Acid Sequence
Platelet Membrane Glycoproteins
Cyanogen Bromide
Serratia marcescens
Gene Duplication
Protein S
Threonine
Leucine
Trypsin
Serine
Sequence Analysis
Staphylococcus aureus
Glycoproteins
Peptide Hydrolases
Complementary DNA
Carbohydrates
Peptides

ASJC Scopus subject areas

  • General
  • Genetics

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Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. / Titani, K.; Takio, K.; Handa, M.; Ruggeri, Z. M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 84, No. 16, 1987, p. 5610-5614.

Research output: Contribution to journalArticle

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N2 - We report the amino acid sequence of a 299-residue segment from the α chain of the human platelet membrane glycoprotein Ib. This includes the complete sequence of the amino-terminal cryptic 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 fllowing 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 α-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 glycosated (at serine and threonine residues) region corresponding to the previously described 'macroglycopeptide' and representing the carboxyl-terminal half of the α chain is likely to begin at residue 292. The determined sequence of the α chain of glycoprotein Ib contains a region (residues 29-193) with seven repeats, which is indication of gene duplication and is highly homologous to human leucine-rich α2-glycoprotein. This protein sequence agrees completely with that deduced from the cDNA sequence reported by Lopez et al.

AB - We report the amino acid sequence of a 299-residue segment from the α chain of the human platelet membrane glycoprotein Ib. This includes the complete sequence of the amino-terminal cryptic 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 fllowing 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 α-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 glycosated (at serine and threonine residues) region corresponding to the previously described 'macroglycopeptide' and representing the carboxyl-terminal half of the α chain is likely to begin at residue 292. The determined sequence of the α chain of glycoprotein Ib contains a region (residues 29-193) with seven repeats, which is indication of gene duplication and is highly homologous to human leucine-rich α2-glycoprotein. This protein sequence agrees completely with that deduced from the cDNA sequence reported by Lopez et al.

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