The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function

EMBO J. 1989 May;8(5):1361-8.

Abstract

VLA-4 is a cell surface heterodimer in the integrin superfamily of adhesion receptors. Anti-VLA-4 antibodies inhibited cytolytic T cell activity, with inhibitory activity directed against the effector T cells rather than their targets. Thus, whereas other VLA receptors appear to mediate cell--matrix interactions, VLA-4 may have a cell--cell adhesion function. To facilitate comparative studies of VLA-4 and other integrins, cDNA clones for the human alpha 4 subunit of VLA-4 were selected and then sequenced. The 3805 bp sequence encoded for 999 amino acids, with an N-terminus identical to that previously obtained from direct sequencing of purified alpha 4 protein. The alpha 4 amino acid sequence was 17-24% similar to other integrin alpha chains with known sequences. Parts of the alpha 4 sequence most conserved in other alpha chains include (i) the positions of 19/24 cysteine residues, (ii) three potential divalent cation binding sites of the general structure DXDXDGXXD and (iii) the transmembrane region. However, alpha 4 stands apart from all other known integrin alpha subunit sequences because (i) alpha 4 has neither an inserted I-domain, nor a disulfide-linked C-terminal fragment, (ii) its sequence is the most unique and (iii) only alpha 4 has a potential protease cleavage site, near the middle of the coding region, which appears responsible for the characteristic 80,000 and 70,000 Mr fragments of alpha 4.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Differentiation / genetics*
  • Antigens, Surface / genetics
  • Base Sequence
  • Cell Adhesion
  • Cell Adhesion Molecules
  • DNA / genetics
  • Humans
  • Integrins
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Protein Conformation
  • Receptors, Immunologic / genetics
  • Receptors, Very Late Antigen
  • Sequence Homology, Nucleic Acid
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Differentiation
  • Antigens, Surface
  • Cell Adhesion Molecules
  • Integrins
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Receptors, Very Late Antigen
  • DNA

Associated data

  • GENBANK/X15356