Although alanine substitutions at sites 269, 270, 271 and 277 have been investigated in two studies [9, 10] , detailed studies on the functional structure of the ''turn'' (Gln 269 -Arg 277 ) between a-H and a-I were limited. In our previous study on hepatitis B virus RT, conserved residues located at the ''turn'' of helix clamp motif were found important for pregenomic RNA encapsidation during the assembly of nucleocapsids [15, 16] . Since this homologous helix clamp motif is also present in HIV-1 RT, we hypothesized that residues in the turn may play important roles in viral life cycle. Our recent study showed that alanine substitutions at 271 and 274 of HIV-1 RT drastically affected viral replication, but discordance between viral replication and RT activity was observed [17] . In this study, we confirmed our previous observations and further investigated why the two mutations abrogated viral replication. Our study demonstrated that these two mutations lead to rapid degradation of RT in viral particles, indicating that the residues of 271 and 274 are critical for maintaining the stability of HIV RT.