Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes.

ABSTRACT: Cryptic pockets are of growing interest as potential drug targets, particularly to control protein-nucleic acid interactions that often occur via flat surfaces. However, it remains unclear whether cryptic pockets contribute to protein function or if they are merely happenstantial features that can easily be evolved away to achieve drug resistance. Here, we explore whether a cryptic pocket in the Interferon Inhibitory Domain (IID) of viral protein 35 (VP35) of Zaire ebolavirus aids its ability to bind double-stranded RNA (dsRNA). We use simulations and experiments to study the relationship between cryptic pocket opening and dsRNA binding of the IIDs of two other filoviruses, Reston and Marburg. These homologs have nearly identical structures but block different interferon pathways due to di

SUBMITTER: Mallimadugula UL 

PROVIDER: S-EPMC11370563 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature