Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide.

ABSTRACT: Incorporation of chemical modifications into small interfering RNAs (siRNAs) increases their metabolic stability and improves their tissue distribution. However, how these modifications impact interactions with Argonaute-2 (Ago2), the molecular target of siRNAs, is not known. Herein we present the crystal structure of human Ago2 bound to a metabolically stable siRNA containing extensive backbone modifications. Comparison to the structure of an equivalent unmodified-siRNA complex indicates that the structure of Ago2 is relatively unaffected by chemical modifications in the bound siRNA. In contrast, the modified siRNA appears to be much more plastic and shifts, relative to the unmodified siRNA, to optimize contacts with Ago2. Structure-activity analysis reveals that even major conformational

SUBMITTER: Schirle NT 

PROVIDER: S-EPMC4993527 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature