HUMAN PLATELET GLYCOPROTEIN-V - CHARACTERIZATION OF THE POLYPEPTIDE AND THE RELATED IB-V-IX RECEPTOR SYSTEM OF ADHESIVE, LEUCINE-RICH GLYCOPROTEINS

Human platelet glycoprotein (GP) V (M(r) 83,300), whose primary struct ure is reported here, is a part of the Ib-V-IX system of surface glyco proteins (GPs Ibalpha, Ibbeta, V, IX) that constitute the receptor for von Willebrand factor (vWf) and mediate the adhesion of platelets to injured vascular surfaces in the arterial circulation, a critical init iating event in hemostasis. System members share physical associations , leucine-rich glycoprotein (LRG) structures, and a congenital deficie ncy state, Bernard-Soulier syndrome. With PCR techniques and platelet cDNA templates, 1.4 kb of GP V cDNA sequence was obtained that encodes 469 GP V amino acids. A genomic 3.5-kb BamHI fragment was then isolat ed that includes 3.46 kb of GPV cDNA sequence: the 1.7-kb open reading frame plus 2 bases of the 5' and 1.8 kb of the 3' untranslated region s. Northern blot analysis reveals three GP V platelet transcripts of 3 .8, 4.2, and 5.2 kb. A 16-amino acid signal peptide is present. Mature GP V is a 544-amino acid transmembrane protein with a 504-amino acid extracellular domain that encompasses a set of 15 tandem LRG repeats i n a ''flank-LRG center-flank'' array [Roth, G. J. (1991) Blood 77, 5-1 9] along with eight putative N-linked glycosylation sites and cleavage sites for thrombin and calpain. GP V is a transmembrane, adhesive LRG protein that plays an undefined, but potentially critical, role in th e expression and/or function of the Ib-V-IX receptor for vWf/shear-dep endent platelet adhesion in arteries.