A Proton-Coupled Dynamic Switch in the HIV-1 Dimerization Initiation Site Kissing Complex
M Mihailescu, John Marino
In human immunodeficiency virus type 1 (HIV-1), the dimerization initiation site (DIS) is the sequence primarily responsible for initiating the non-covalent linkage of two homologous strands of genomic RNA during viral assembly. The DIS loop contains an auto-complementary hexanucleotide sequence and forms a symmetric homodimer through a loop-loop kissing interaction. In a structural rearrangement catalyzed by the HIV-1 nucleocapsid protein (NCp7) and suggested to be associated with maturation of the budded viral particle, DIS converts from a kissing dimmer to an extended duplex. Here, we demonstrate that the DIS kissing dimmer displays localized conformational dynamics that result from the specific protonation of the NI base nitrogen of DIS loop reside A272 at near physiological pH. The rate of NCp7 catalyzed maturation of the DIS kissing dimmer is also shown to directly correlate with the observed proton-coupled dynamics, where NCp7 is found to convert the more dynamic A272 protonated state with a faster rate. Our results reveal a novel role for base protonation in modulating RNA structure and suggest a mechanism for regulating NCp7 catalyzed maturation of HIV-1 genomic RNA.
Proceedings of the National Academy of Sciences of the United States of America
and Marino, J.
A Proton-Coupled Dynamic Switch in the HIV-1 Dimerization Initiation Site Kissing Complex, Proceedings of the National Academy of Sciences of the United States of America
(Accessed June 9, 2023)