Domain-elongation NMR spectroscopy yields new insights into RNA dynamics and adaptive recognition

Abstract

By simplifying the interpretation of nuclear magnetic resonance spin relaxation and residual dipolar couplings data, recent developments involving the elongation of RNA helices are providing new atomic insights into the dynamical properties that allow RNA structures to change functionally and adaptively. Domain elongation, in concert with spin relaxation measurements, has allowed the detailed characterization of a hierarchical network of local and collective motional modes occurring at nanosecond timescale that mirror the structural rearrangements that take place following adaptive recognition. The combination of domain elongation with residual dipolar coupling measurements has allowed the experimental three-dimensional visualization of very large amplitude rigid-body helix motions in HIV-1 transactivation response element (TAR) that trace out a highly choreographed trajectory in which the helices twist and bend in a correlated manner. The dynamic trajectory allows unbound TAR to sample many of its ligand bound conformations, indicating that adaptive recognition occurs by “conformational selection” rather than “induced fit.” These studies suggest that intrinsic flexibility plays essential roles directing RNA conformational changes along specific pathways.