KCS

Gene silencing through RNA interference (RNAi) is carried out by RNA-induced silencing complex (RISC). Argonate proteins are key components of the RISC. Argonaute is composed of four different domains including PAZ and PIWI domains. PAZ domain binds at 3’end of the siRNA and PIWI domain is similar to RNase H which cleaves the target mRNA. Argonaute contributes to “Slicer” activity of RISC, providing the catalytic engine for RNAi. The PAZ domain is a RNA-binding module found in Argonaute and some Dicer proteins and its structure has been determined in the free-state. Although it is reported that there are four different of Human Argonautes (hAgo), RISC including hAgo2 can only cleave target mRNA catalytically. The active site is made up of a unique Asp-Asp-His (DDH) motif. To find critical amino acids in hAgo2, various sequence alignments were carried out with Agonautes from various sources. Finally, 3D structure of hAgo2 protein was constructed using homology modeling methods and the structure was compared and analyzed to find out the key features of the hAgo2 structure.