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


CONCLUSIONS
Overall, low-frequency vibrations of Argonaute are consistent with mechanisms within the current reaction cycle model for RNA interference.
Ming
Dengming
D
Computer, Computational, and Statistical Sciences Division, Los Alamos National Laboratory, Los Alamos, USA. dming@lanl.gov
Wall
Michael E
ME
Sanbonmatsu
Kevin Y
KY
D019843:Archaeal Proteins / Q000737:chemistry / Q000648:ultrastructure*; D019611:Archaeoglobus fulgidus / Q000201:enzymology / Q000235:genetics; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D020027:Pyrococcus furiosus / Q000201:enzymology / Q000235:genetics; D012313:RNA / Q000737:chemistry; D034622:RNA Interference / Q000502:physiology; D034743:RNA-Induced Silencing Complex / Q000737:chemistry* / Q000648:ultrastructure*; D013816:Thermodynamics; D054159:Torsion, Mechanical; D014732:Vibration
D019843:Archaeal Proteins; D034743:RNA-Induced Silencing Complex; D012313:RNA