Comparative structural insights and functional analysis for the distinct unbound states of Human AGO proteins.

ABSTRACT: The four human Argonaute (AGO) proteins, critical in RNA interference and gene regulation, exhibit high sequence and structural similarity but differ functionally. We investigated the underexplored structural relationships of these paralogs through microsecond-scale molecular dynamics simulations. Our findings reveal that AGO proteins adopt similar, yet unsynchronized, open-close states. We observed similar and unique local conformations, interdomain distances and intramolecular interactions. Conformational differences at GW182/ZSWIM8 interaction sites and in catalytic/pseudo-catalytic tetrads were minimal. Tetrads display conserved movements, interacting with distant miRNA binding residues. We pinpointed long common protein subsequences with consistent molecular movement but varying solve

SUBMITTER: Kakoulidis P 

PROVIDER: S-EPMC11923369 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature