Novel Insights into Guide RNA 5'-Nucleoside/Tide Binding by Human Argonaute 2.

ABSTRACT: The human Argonaute 2 (hAgo2) protein is a key player of RNA interference (RNAi). Upon complex formation with small non-coding RNAs, the protein initially interacts with the 5'-end of a given guide RNA through multiple interactions within the MID domain. This interaction has been reported to show a strong bias for U and A over C and G at the 5'-position. Performing molecular dynamics simulations of binary hAgo2/OH-guide-RNA complexes, we show that hAgo2 is a highly flexible protein capable of binding to guide strands with all four possible 5'-bases. Especially, in the case of C and G this is associated with rather large individual conformational rearrangements affecting the MID, PAZ and even the N-terminal domains to different degrees. Moreover, a 5'-G induces domain motions in the protein

SUBMITTER: Kalia M 

PROVIDER: S-EPMC4730269 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature