Human T-cell leukemia virus type 1 envelope glycoprotein gp21 (HTLV-1 gp21)

The Human T-cell leukemia virus type 1 (HTLV-1) envelope glycoprotein gp21 is the transmembrane (TM) subunit responsible for mediating the fusion of viral and host cell membranes (UniProt P03381). Following the binding of the surface subunit (gp46) to host receptors like GLUT1 or NRP1, gp21 undergoes a significant conformational change to form a stable trimer-of-hairpins or six-helix bundle (6HB) (PMID: 15105485). This structural transition, involving the interaction of N-terminal and C-terminal heptad repeat regions (NHR and CHR), provides the energy required to pull the viral and cellular membranes together for pore formation (PMID: 22496731). As a Class I viral fusion protein, gp21 is a critical therapeutic target for preventing HTLV-1 infection and its associated pathologies, such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM/TSP). Experimental strategies focus on fusion inhibitors, primarily synthetic peptides derived from the heptad repeat sequences that competitively bind to gp21 intermediates and block 6HB assembly (PMID: 30366001). Despite its potential, challenges remain regarding the delivery and metabolic stability of these peptide-based inhibitors in clinical settings.

Other names

gp21Transmembrane glycoprotein gp21HTLV-1 TM subunitHTLV-1 Env gp21HTLV-1 envelope protein transmembrane subunit

Fusion inhibition by preventing the formation of the six-helix bundle (trimer-of-hairpins) structure.