Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

New Insights: Structure and behavior of the sarcin-ricin ribosomal RNA motif ? molecular dynamics simulations

The sarcin-ricin domain (SRD) is a highly conserved component of 23S-28S rRNA from the large ribosomal subunit. The SRD motif represents a crucial site for the binding of elongation factors. The SRD motif consists of GAGA tetraloop, G-bulged cross-strand A-stack, flexible region and duplex part. We carried out explicit solvent molecular dynamics (MD) simulations for SRD motifs from 23S (E. coli) and 28S (rat) rRNAs and analyzed the overall dynamics, base pairing, hydration, cation binding and other SRD features in detail. The SRD is surprisingly static in multiple 25 ns long simulations and lacks any non-local motions, with RMSd values between averaged MD and high-resolution X-ray structures 1-1.4 Å. Modest dynamics is observed in the tetraloop, namely, rotation of adenine in its apex and subtle reversible shift of the tetraloop with respect to the adjacent base pair. The deformed flexible region in low-resolution rat X-ray structure is repaired by simulations. The simulations reveal few flips of backbone torsion angles, which do not affect positions of bases and do not indicate a force field imbalance. Non-Watson-Crick base pairs are rigid and mediated by long-residency water molecules while there are several modest cation-binding sites around SRD. In summary, SRD is an unusually stiff rRNA building block. Its intrinsic structural and dynamical signatures seen in simulations are strikingly distinct from other rRNA motifs such as Loop E and Kink-turns. In a sharp contrast to Loop E (and other RNAs like kissing-loop complex and hepatitis delta virus ribozyme), SRD is not associated with any deep electrostatic potential pockets and is not a major cation-binding motif.

References and Footnotes
  1. N. Spackova, J. Sponer. Molecular dynamics simulations of sarcin-ricin rRNA motif. Nucleic Acids Research 34, 697-708 (2006).

Nada Spackova and
Jiri Sponer

Institute of Biophysics,
Acad. of Sciences
Kralovopolska 135,
61265 Brno, Czech Republic

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