Specific recognition of primer tRNA Lys3 by HIV-1 nucleocapsid protein: involvement of the zinc fingers and the N-terminal basic extension

Abstract

Reverse transcription of HIV-1 viral RNA uses human tRNA Lys 3 as a primer. We have previously characterised the structural aspects of the tRNA Lys 3 interaction by NMR. In HIV-1 virions, the nucleocapsid protein NCp7 contains two zinc fingers flanked by basic residues. Using NMR, the respective role of the N-terminal residues and the zinc fingers in the interaction with tRNA Lys 3/ 12-53 NCp7 was investigated by studying the tRNA Lys 3 and tRNA Lys 3/ 1-55 NCp7 complexes. The N-terminal basic residues do not change the footprint of NC on tRNA Lys 3/Cys 23 12-53 NCp7 but strengthen the binding whereas the mutation of the zinc-binding histidine at position 23 that was shown to result in non-infectious particles prevents the interaction with the first bases of the acceptor stem.