Dissect Conformational Distribution and Drug-Induced Population Shift of Prokaryotic rRNA A‑Site

The dynamic behavior of the rRNA A-site plays an important functional role. We have employed femtosecond time-resolved spectroscopy to investigate the nature of the conformational dynamics. In the drug-free state, the A-site samples multiple distinct conformations. Drug binding shifts the population distribution in a drug-specific manner. Motions of bases on nanosecond and picosecond time scales are differentially affected by the drug binding. Our results underscore the importance of understanding the detailed dynamic picture of molecular recognition by resolving dynamics in the distinct picosecond time regime and facilitate development of antimicrobial drugs targeting dynamic RNAs

NMR Structures and Dynamics in a Prohead RNA Loop that Binds Metal Ions

Metal ions are critical for RNA structure and enzymatic activity. We present the structure of an asymmetric RNA loop that binds metal ions and has an essential function in a bacteriophage packaging motor. Prohead RNA is a noncoding RNA that is required for genome packaging activity in phi29-like bacteriophage. The loops in GA1 and phi29 bacteriophage share a conserved adenine that forms a base triple, although the structural context for the base triple differs. NMR relaxation studies and femtosecond time-resolved fluorescence spectroscopy reveal the dynamic behavior of the loop in the metal ion bound and unbound forms. The mechanism of metal ion binding appears to be an induced conformational change between two dynamic ensembles rather than a conformational capture mechanism. These results provide experimental benchmarks for computational models of RNA–metal ion interactions