Chirality-Dependent Amino Acid Modulation of RNA Folding
mediaposted on 2020-12-09, 19:41 authored by David A. Nicholson, Abhigyan Sengupta, David J. Nesbitt
The preponderance of a specific d- or l-chirality in fats, sugars, amino acids, nucleic acids, and so on is ubiquitous in nature, yet the biological origin of such chiral dominance (i.e., with one enantiomer overwhelmingly present) remains an open question. One plausible proposal for the predominance of l-chirality in amino acids could be through evolutionary templating of chiral RNA-folding via chaperone activity. To help evaluate this possibility, single molecule fluorescence experiments have been performed that measure the chiral dependence of chaperone folding dynamics for the simple tetraloop–tetraloop receptor (TL-TLR) tertiary binding motif in the presence of a series of chiral amino acids. Specifically, d- vs l-arginine is found to accelerate the unfolding of this RNA motif in a chirally selective fashion, with temperature-dependent studies of the kinetics performed to extract free energy, enthalpy, and entropy landscapes for the underlying thermodynamics. Furthermore, all-atom molecular dynamics (MD) simulations are pursued to provide additional physical insight into this chiral sensitivity, which reveal enantiomer-specific sampling of nucleic acid surfaces by d- vs l-arginine and support a putative mechanism for chirally specific denaturation of RNA tertiary structure by arginine but not other amino acids.