Dynamics and energetics of PCBP1 binding to severely oxidized RNA.

ABSTRACT: Oxidatively generated lesions such as 8-oxo-7, 8-dihydroguanine (8-oxoG) on RNA strands constitute a hallmark marker of the oxidative stress in the cell. Poly-C binding protein 1 (PCBP1) is able to specifically recognize severely damaged RNA strands containing two 8-oxoG lesions separated by five nucleobases, which trigger a signaling pathway leading to cell apoptosis. We apply an in silico protocol based on microsecond timescale all-atom classical molecular dynamics simulations associated with conformational and energy analyses to unveil the specific recognition mechanism at a molecular level. By comparing the RNA and protein behavior for sequences with six different damage profiles, our results highlight an allosteric mechanism, allowing a stronger binding of the oxidized guanine

SUBMITTER: Gillet N 

PROVIDER: S-EPMC9671708 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature