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Extended structures in RNA folding intermediates are due to non-native interactions rather than electrostatic repulsion.
J Mol Biol. 2010 Feb 23;
Authors: Baird NJ, Gong H, Zaheer SS, Freed KF, Pan T, Sosnick TR
RNA folding occurs via a series of transitions between metastable intermediate states for Mg(2+) concentrations below those needed to fold the native structure. In general, these folding intermediates are considerably less compact than their respective native states. Our previous work demonstrates that the major equilibrium intermediate of the 154 residue specificity domain (S-domain) of the B. subtilis RNase P RNA is more extended than its native structure. We now investigate two models with falsifiable predictions regarding the origins of the extended intermediate structures in the S-domains of the B. subtilis and the E. coli RNase P RNA that belong to different classes P RNA and have distinct native structures. The first model explores the contribution of electrostatic repulsion, while the second model probes specific interactions in the core of the folding intermediate. Using small-angle X-ray scattering (SAXS) and Langevin Dynamics (LD) simulations, we show that electrostatics only plays a minor role, whereas specific interactions largely accounts for the extended nature of the intermediate. Structural contacts in the core, including a non-native base-pair, help to stabilize the intermediate conformation. We conclude that RNA folding intermediates adopt extended conformations due to short-range, non-native interactions rather than generic electrostatic repulsion of helical domains. These principles apply to other ribozymes and riboswitches that undergo functionally relevant conformational changes.
PMID: 20188108 [PubMed - as supplied by publisher]