The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence.

Abstract

The primary structure of the (3 chain of human glycoprotein lb (GPIb), the platelet receptor for von Willebrand factor, has been established by a combination of cDNA cloning and amino acid sequence analysis. A A phage cDNA expression library prepared from human erythroleukemia cells (HEL cells) was screened with a radiolabeled affinitypurified rabbit polyclonal antibody to the ( chain of GPIb. Eighteen positive clones were isolated and plaque-purifiled and the nucleotide sequences of three were determined. The composite sequence spanned 968 nucleotides and included a 5' untranslated region of 22 nucleotides, an open reading frame of 618 nucleotides encoding a signal peptide of 28 amino acids and a mature protein of 181 amino acids, a stop codon, and a 3' noncoding region of 307 nucleotides. The 3' noncoding sequence also contained a polyadenylylation signal (AATAAA) 14 nucleotides upstream from the poly(A) tail of 18 nucleotides. Edman degradation of the intact P chain and of peptides produced by chemical cleavage yielded amino acid sequences spanning 76 residues that were identical to those predicted from the cDNA. The amino-terminal region of the (3 chain contains a leucine-rich sequence of 24 amino acids that is similar to a sequence that occurs as seven tandem repeats in the a chain of GPIb and nine tandem repeats in leucine-rich a2-glycoprotein. The leucine-rich sequence in the P chain of GPIb is flanked on both sides by amino acid sequences that are similar to those flanking the leucine-rich tandem repeats of the a chain of GPIb and leucine-rich a2-glycoprotein. The aminoterminal region of the (3 chain of GPIb is followed by a transmembrane segment of 25 amino acids and an intracellular segment of 34 amino acids at the carboxyl terminus of the protein. The intracellular segment contains an unpaired cysteine and two potential sites for phosphorylation by cAMPdependent protein kinase.

Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo.

“…This clustering of mutations prompted us to examine the carboxy-terminal flanking sequences of other L-rich repeat-containing proteins more closely. In Toil, both blocks of L-rich repeats are followed by a cysteine-containing motif, which is also found in a subset of proteins that have extracellular Lrich repeats including L-rich glycoprotein {Takahashi et al 1985}, the platelet transmembrane proteins gp lb and 13, gp IX (Lopez et al 1987(Lopez et al , 1988Hickey et al 1989}, and the lutropin-choriogonadotropin receptor (McFarland et al 1989}. We found that the similarity between these motifs extends further than described previously {Hickey et Keith and Gay 1990} and that the motifs contain four, rather than only two, conserved cysteine residues {Fig.…”

“…The 803-amino acid residue extracellular domain, of Toll is composed largely of two blocks of leucine-rich (L-rich) repeats. L-rich repeats of this type have been found in a diverse group of proteins including the transmembrane protein platelet protein glycoprotein (gp) lb ~ and f3, gp IX, and the lutropinchoriogonadotropin receptor (Lopez et al 1987(Lopez et al , 1988Hickey et al 1989;McFarland et al 1989). The Drosophila protein chaoptin, which is composed almost exclusively of L-rich repeats, can mediate homotypic cell adhesion (Krantz and Zipursky 1990), and Toll itself can promote heterotypic cell adhesion (Keith and Gay 1990), providing evidence that this motif defines a protein-protein interaction domain.…”

Bernard‐Soulier syndrome Karlstad: Trp 498→Stop mutation resulting in a truncated glycoprotein Ibα that contains part of the transmembranous domain

“…The 145 kD GPIba contains von Willebrand factor (VWF) and thrombin binding sites and is linked to the 27 kD GPIbb by a disulphide bond. The 22 kD GPIX is noncovalently bound and GPV is more weakly associated (Lopez et al, 1987(Lopez et al, , 1988Hickey et al, 1989;Modderman et al, 1992).…”

Viscoelasticity and Ultrastructure in Coagulation and Inflammation: Two Diverse Techniques, One Conclusion

“…Von Willebrand factor acts as a bridge between the platelets and the injury site [ 62 , 63 ] as it binds to specific receptors, namely glycogprotein Ib/glycoprotein IX, on the surface of activated platelets as well as the subendothelium [ 64 ]. Similarly, fibrinogen also acts a platelet-platelet bridge as it binds to the surface receptors glycoprotein IIb/IIIa on adjoining activated platelets [ 65 , 66 ].…”