Internal Dynamics of the Homotrimeric HIV‐1 Viral Coat Protein gp41 on Multiple Time Scales

Fusion of viral and cellular membranes is elicited by the HIV-1 envelope glycoprotein gp120/gp41. The precursor gp160, encoded by the Env gene, is cleaved post-translationally into two chains, gp120 and gp41, which remain non-covalently associated as a homotrimer of heterodimers and form a spike on the viral surface.[1] Upon CD4 recognition, the gp120 subunit dissociates from gp41, which remains anchored through its C-terminal transmembrane helix (TM) in the viral membrane. After gp120 dissociation, the N-terminal fusion peptide of gp41 is exposed and can insert into the host cell membrane.[2] Because of its high sequence conservation and its accessibility to the humoral immune system,[3] gp41 represents an attractive drug target for antiviral therapy as well as a key player in vaccine research.[4, 5]