Packaging HIV virion components through dynamic equilibria of a human tRNA synthetase.
Aminoacyl tRNA synthetases, components of the translation apparatus, have alternative functions outside of translation. The structural and mechanistic basis of these alternative functions is of great interest. As an example, reverse transcription of the HIV genome is primed by a human lysine-specific tRNA (tRNA(Lys3)) that is packaged (into the virion) by the HIV Gag protein with lysyl-tRNA synthetase (LysRS). Not understood is the structural basis for simultaneous packaging of tRNA(Lys3), LysRS, and Gag. Here, ab initio computational methods, together with our recent high-resolution 3-D structure of human LysRS, produced an energy-minimized model where Gag, tRNA(Lys), and LysRS form a ternary complex. Interestingly, the model requires normally homodimeric LysRS to dissociate into a monomer that bridges between Gag and tRNA(Lys3). Earlier experiments of others and new experiments presented here, which tested an engineered dissociated form of LysRS, were consistent with the ab initio "bridging monomer" model. The results support an emerging theme that alterative functions of tRNA synthetases may come, in part, from protein surfaces exposed by dynamic equilibria.
The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Min
M
Guo
Ryan
R
Shapiro
Garrett M
GM
Morris
Xiang-Lei
XL
Yang
Paul
P
Schimmel
D000604:Amino Acyl-tRNA Synthetases / Q000502:physiology*; D006678:HIV; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019065:Virus Assembly
D000604:Amino Acyl-tRNA Synthetases