Tetraspanins: An Important Glycoprotein

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Tetraspanins also known as tetraspans or the transmembrane 4 superfamily (TM4SF) are type III membrane glycoproteins which span the plasma membrane four times found in all multicellular eukaryotes. They consist of four transmembrane domains, intracellular N- and C-termini and two extracellular domains, one short (called the small extracellular domain or loop, SED/SEL or EC1) and one long, usually 100 amino acid residues (the large extracellular domain/loop, LED/LEL or EC2) that is subdivided into a constant region containing various protein-protein interaction sites. An important structural feature of the superfamily is the “tetraspanin fold” of the larger extracellular loop (LEL). Here, disulfide bonding of four absolutely conserved cysteines form a subloop structure encompassing a region which is hypervariable between family members and between species homologues of the same tetraspanin. The cysteines are present in three variously conserved motifs: CysCysGly, ProXSerCys (where X = any amino acid) and GluGlyCys, wherein the flexibility and constraint imparted by the conserved Gly residue in CysCysGly and by Pro in ProXSerCys contribute to subloop formation. The region of the LEL outside of this subloop shows better structural conservation, developing three α-helices which not only form a structural platform to present the tetraspanin fold but may also act as an independent contributer to tetraspanin function. The large extracellular loop (LEL) of tetraspanins has been given most attention because it contains functionally important sites like sequence QRD (194–196) in CD151 that is important for association with integrins and is functionally important for integrin-dependent cell spreading and multicellular cable formation. A pos... ... middle of paper ... ...r SDS. Tetraspanins have been recognized as the targets of antibodies which obstruct the infection of a range of viruses. But, it appears that at least two tetraspanins may be involved in HTLV-1 infection and at least four in HIV-1 infection. Thus, it is postulated that quite a lot of tetraspanins will be involved in some or all of the viral life cycles already known and yet to be discovered. Tetraspanins are also famous for their roles in the pathology of infectious diseases such as diphtheria, malaria, and numerous viral infections. From literature, we know that specific tetraspanin family members are selectively linked with particular viruses and affect several stages of infectivity, from initial cellular attachment to syncytium formation and viral particle release concluding that the relationship of tetraspanins with viruses look like it is particularly complex.

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