Cloning of the murine platelet glycoprotein Ibalpha gene highlighting species-specific platelet adhesion.
We report the sequence of a 2,779 base pari genomic DNA fragment containing the mouse glycoprotein (GP) Ibalpha gene. Similar to its human counterpart, the mouse GP Ibalpha gene contains a single exon encoding a 734-residue GP Ibalpha precursor polypeptide. Comparative analysis between human and mouse polypeptides reveals a 75% sequence similarity between the amino-terminal domain of each polypeptide. However, there is sequence divergence within a short linear sequence of the amino-terminal domain previously implicated in human GP Ibalpha as critical for the binding of human von Willebrand factor (vWF). Mouse and human primary sequences diverge through their extracytoplasmic macroglycopeptide domains reducing the overall sequence similarity to 70%. The transmembrane and cytoplasmic sequences are highly conserved in both species with 59 identical residues among the 62 comprising the carboxyl-terminus of each polypeptide. The species-specific interaction between human GP Ibalpha and vWF was demonstrated in a model flow system monitoring the ability of surface-bound human vWF to capture from flowing blood normal mouse platelets or transgenic mouse platelets expressing the human GP Ibalpha subunit. The results further define the structural elements necessary for the interaction of human vWF and platelets.
Ware
J
J
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. jware@scripps.edu
Russell
S
S
Ruggeri
Z M
ZM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014841:von Willebrand Factor / Q000378:metabolism / Q000494:pharmacology
D019038:Platelet Glycoprotein GPIb-IX Complex; D011994:Recombinant Proteins; D014841:von Willebrand Factor