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Open Access Highly Accessed Research article

Domain motions of Argonaute, the catalytic engine of RNA interference

Dengming Ming1, Michael E Wall123 and Kevin Y Sanbonmatsu4*

Author Affiliations

1 Computer, Computational, and Statistical Sciences Division, Los Alamos National Laboratory, Los Alamos, USA

2 Bioscience Division, Los Alamos National Laboratory, Los Alamos, USA

3 Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, USA

4 Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, USA

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BMC Bioinformatics 2007, 8:470  doi:10.1186/1471-2105-8-470

Published: 30 November 2007

Abstract

Background

The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target. Visual inspection of static crystal structures already has enabled researchers to suggest conformational changes of Argonaute that might occur during RNA interference. We have taken the next step by performing an all-atom normal mode analysis of the Pyrococcus furiosus and Aquifex aeolicus Argonaute crystal structures, allowing us to quantitatively assess the feasibility of these conformational changes. To perform the analysis, we begin with the energy-minimized X-ray structures. Normal modes are then calculated using an all-atom molecular mechanics force field.

Results

The analysis reveals low-frequency vibrations that facilitate the accommodation of RNA duplexes – an essential step in target recognition. The Pyrococcus furiosus and Aquifex aeolicus Argonaute proteins both exhibit low-frequency torsion and hinge motions; however, differences in the overall architecture of the proteins cause the detailed dynamics to be significantly different.

Conclusion

Overall, low-frequency vibrations of Argonaute are consistent with mechanisms within the current reaction cycle model for RNA interference.