The inner loop of tetraspanins CD82 and CD81 mediates interactions with human T cell lymphotrophic virus type 1 Gag protein.
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.
Mazurov
Dmitriy
D
HIV Drug Resistance Program, NCI-Frederick, Frederick, Maryland 21702-1201, USA.
Heidecker
Gisela
G
Derse
David
D
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D015683:Gene Products, gag / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051861:Kangai-1 Protein / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D021962:Membrane Microdomains / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary / Q000235:genetics; D060225:Tetraspanin 28
D015703:Antigens, CD; C554798:CD81 protein, human; C497688:CD82 protein, human; D015683:Gene Products, gag; D051861:Kangai-1 Protein; D060225:Tetraspanin 28