Primary structure of the leukocyte function-associated molecule-1α subunit: An integrin with an embedded domain defining a protein superfamily

Abstract

The leukocyte function-associated molecule 1 (LFA-1, CD11a/CD18) is a membrane glycoprotein which functions in cell-cell adhesion by heterophilic interaction with intercellular adhesion molecule 1 (ICAM-1). LFA-1 consists of an α subunit (M(r) = 180,000) and a β subunit (M(r) = 95,000). We report the molecular biology and protein sequence of the α subunit. Overlapping cDNAs containing 5,139 nucleotides were isolated using an oligonucleotide specified by tryptic peptide sequence. The mRNA of 5.5 kb is expressed in lymphoid and myeloid cells but not in a bladder carcinoma cell line. The protein has a 1,063-amino acid extracellular domain, a 29-amino acid transmembrane region, and a 53-amino acid cytoplasmic tail. The extracellular domain contains seven repeats. Repeats V-VII are in tandem and contain putative divalent cation binding sites. LFA-1 has significant homology to the members of the integrin superfamily, having 36% identity with the Mac-1 and p150,95 α subunits and 28% identity with other integrin α subunits. An insertion of ~ 200 amino acids is present in the NH2-terminal region of LFA-1. This 'inserted/interactive' or I domain is also present in the p150,95 and Mac-1 α subunits but is absent from other integrin α subunits sequenced to date. The I domain has striking homology to three repeats in human von Willebrand factor, two repeats in chicken cartilage matrix protein, and a region of complement factor B. These structural features indicate a bipartite evolution from the integrin family and from an I domain family. These features may also correspond to relevant functional domains.