Poster abstracts

Poster number 22 submitted by Andrew Stelzer

Stereoviews of RNA by Inverse Domain Elongation

Andrew Stelzer (Department of Chemistry The University of Michigan), Qi Zhang (Department of Chemistry The University of Michigan), Hashim Al-Hahsimi (Department of Chemsitry and Biophysics The University of Michigan)

Abstract:
Internal motions in RNA can be decoupled from overall reorientation by elongating a given reference domain using unlabelled Watson-Crick residues. Here, we show that by elongating more than one domain it is possible to collect larger amounts of NMR data, including spin relaxation measurements and residual dipolar couplings, which provides a view of dynamics relative to multiple frames of reference. We show that this “inverse” domain elongation approach resurrects sensitivity to twisting motions around axially symmetric domains allowing model-free characterization of motions with complete rotational sensitivity. The multi-domain elongation approach is demonstrated on the HIV-1 Transactivation Response Element (TAR). Results reveal a combination of bending and twisting domain motions that mirror the structural changes that follow adaptive recognition of diverse chemical targets. Implications of results on the rational design of TAR binding anti-HIV therapeutics will also be discussed.

Keywords: residual dipolar couplings, HIV-1 TAR, dynamics