Human T-cell leukemia virus type 2 envelope glycoprotein gp21 (HTLV-2 gp21)

The Human T-cell leukemia virus type 2 (HTLV-2) envelope glycoprotein gp21 is the transmembrane (TM) subunit of the viral envelope, playing a pivotal role in viral entry by mediating membrane fusion (UniProt P03382). It is synthesized as part of the gp61 precursor, which is proteolytically processed into the surface subunit (gp46) and gp21. The fusion process is driven by a transition of gp21 from a metastable pre-fusion state to a stable post-fusion conformation characterized by a six-helix bundle, or trimer-of-hairpins, formed by the interaction of N-terminal and C-terminal heptad repeats (N-HR and C-HR) (Kim et al., 2004). This structural change pulls the viral and host cell membranes into close proximity, facilitating the formation of a fusion pore (Pique & Jones, 2012). While HTLV-2 is often asymptomatic, it is associated with rare neurological conditions similar to HTLV-1-associated myelopathy and may impact immune function in co-infected individuals. The gp21 fusion region is a primary target for the development of fusion inhibitors, typically peptide-based agents that bind to the N-HR coiled-coil and prevent the assembly of the six-helix bundle, thereby blocking viral entry.

Other names

Transmembrane glycoprotein gp21TM subunitHTLV-II gp21Envelope protein gp21gp21 transmembrane protein

Inhibition of viral-cell membrane fusion by binding to the N-terminal heptad repeat (N-HR) region of gp21, thereby preventing the formation of the stable six-helix bundle (trimer-of-hairpins) required for entry (Kim et al., 2004).