The primary structure of the VLA-2/collagen receptor α2 subunit (platelet gpIa): Homology to other integrins and the presence of a possible collagen-binding domain

Abstract

VLA-2 (also called gpIa/IIa on platelets) is a collagen receptor with a unique α subunit and a β subunit common to other adhesion receptors in the VLA/integrin family. Multiple cDNA clones for the human VLA-2 α2 subunit have been selected from a λgtll library by specific antibody screening. The 5,374-bp nucleotide sequence encoded for 1,181 amino acids, including a signal peptide of 29 amino acids followed by a long extracellular domain (1,103 amino acids), a transmembrane domain, and a short cytoplasmic segment (22 amino acids). Direct sequencing of purified α2 protein confirmed the identity of the 15 NH2-terminal amino acids. Overall, the α2 amino acid sequence was 18-25% similar to the sequences known for other integrin α subunits. In particular, the α2 sequence matched other integrin α chains in (a) the positions of 17 of its 20 cysteine residues; (b) the presence of three metal-binding domains of the general structure DXDXDGXXD; and (c) the transmembrane domain sequence. In addition, the α2 sequence has a 191-amino acid insert (called the I-domain), previously found only in leukocyte integrins of the β2 integrin family. The α2 I-domain was 23-41% similar to domains in cartilage matrix protein and von Willebrand factor, which are perhaps associated with collagen binding. The NH2-terminal sequence reported here for α2 does not match the previously reporteed α2 NH2-terminal sequence (Takada, Y., J.L. Strominger, and M.E. Hemler. 1987. Proc. Natl. Acad. Sci. USA. 84:3239-3243). Resolution of this discrepancy suggests that there may be another VLA heterodimer that resembles VLA-2 in size but has a different amino acid sequence.