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Domain motions of Argonaute, the catalytic engine of RNA interference.

Ming D, Wall ME, Sanbonmatsu KY - BMC Bioinformatics (2007)

Bottom Line: The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computer, Computational, and Statistical Sciences Division, Los Alamos National Laboratory, Los Alamos, USA. dming@lanl.gov

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.

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Related in: MedlinePlus

Pair correlations of atomic displacements calculated using Equation (3): (a) Pf-Ago, (b) Aa-Ago. Regions of high (red), medium (green), and low (blue) correlations are shown. Black represents large anti-correlation. The self-correlation (diagonal line) often has the highest value. The area and shape of off-diagonal islands are measures of the extent to which the motions of different domains are correlated.
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Figure 5: Pair correlations of atomic displacements calculated using Equation (3): (a) Pf-Ago, (b) Aa-Ago. Regions of high (red), medium (green), and low (blue) correlations are shown. Black represents large anti-correlation. The self-correlation (diagonal line) often has the highest value. The area and shape of off-diagonal islands are measures of the extent to which the motions of different domains are correlated.

Mentions: To explore the correlated motions among the four domains in the proteins, we calculated the covariance matrices whose elements are defined by Equation (3). Figure 5 shows the contour plots of these matrices. In the contour plot, the diagonal line depicts the self-correlation of the each residue while the off-diagonal points depict the correlations between different residues. The isolated off-diagonal points are associated with higher-frequency and less-collective motions.


Domain motions of Argonaute, the catalytic engine of RNA interference.

Ming D, Wall ME, Sanbonmatsu KY - BMC Bioinformatics (2007)

Pair correlations of atomic displacements calculated using Equation (3): (a) Pf-Ago, (b) Aa-Ago. Regions of high (red), medium (green), and low (blue) correlations are shown. Black represents large anti-correlation. The self-correlation (diagonal line) often has the highest value. The area and shape of off-diagonal islands are measures of the extent to which the motions of different domains are correlated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2238725&req=5

Figure 5: Pair correlations of atomic displacements calculated using Equation (3): (a) Pf-Ago, (b) Aa-Ago. Regions of high (red), medium (green), and low (blue) correlations are shown. Black represents large anti-correlation. The self-correlation (diagonal line) often has the highest value. The area and shape of off-diagonal islands are measures of the extent to which the motions of different domains are correlated.
Mentions: To explore the correlated motions among the four domains in the proteins, we calculated the covariance matrices whose elements are defined by Equation (3). Figure 5 shows the contour plots of these matrices. In the contour plot, the diagonal line depicts the self-correlation of the each residue while the off-diagonal points depict the correlations between different residues. The isolated off-diagonal points are associated with higher-frequency and less-collective motions.

Bottom Line: The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computer, Computational, and Statistical Sciences Division, Los Alamos National Laboratory, Los Alamos, USA. dming@lanl.gov

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.

Show MeSH
Related in: MedlinePlus