The inner loop of tetraspanins CD82 and CD81 mediates interactions with human T cell lymphotrophic virus type 1 Gag protein

J Biol Chem. 2007 Feb 9;282(6):3896-903. doi: 10.1074/jbc.M607322200. Epub 2006 Dec 13.


The tetraspanin superfamily proteins play important roles in organizing membrane protein complexes, modulating integrin function, and controlling T cell adhesion. Tetraspanins such as CD82 contain two extracellular loops with its N terminus, C terminus, and inner loop exposed to the cytoplasm. The matrix (MA) domain of human T cell lymphotrophic virus, type 1 (HTLV-1), Gag interacts with the cytoplasmic face of the plasma membrane and is concentrated at tetraspanin-enriched microdomains. To understand the basis of this association, we generated site-directed mutations in the various domains of CD82 and used coimmunoprecipitation and colocalization approaches to examine interactions with HTLV-1 MA. The large extracellular loop of CD82, which is important for interactions with integrins, was not required for the association with HTLV-1 MA. The cytoplasmic N terminus and C terminus of CD82 were also dispensable for CD82-MA interactions. In contrast, mutations of conserved amino acids in the inner loop of CD82 or of palmitoylated cysteines that flank the inner loop diminished CD82 association with MA. HTLV-1 MA also interacted with the inner loop of CD81. Thus, association of HTLV-1 Gag with tetraspanin-enriched microdomains is mediated by the inner loops of CD81 and CD82.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • Cell Line
  • Gene Products, gag / metabolism*
  • HeLa Cells
  • Human T-lymphotropic virus 1 / chemistry*
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Jurkat Cells
  • Kangai-1 Protein / chemistry*
  • Kangai-1 Protein / genetics
  • Kangai-1 Protein / physiology*
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / genetics
  • Membrane Microdomains / physiology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary / genetics
  • Tetraspanin 28


  • Antigens, CD
  • CD81 protein, human
  • CD82 protein, human
  • Gene Products, gag
  • Kangai-1 Protein
  • Tetraspanin 28