Unveiling Cas8 dynamics and regulation within a transposon-encoded Cascade-TniQ complex.

ABSTRACT: The Vibrio cholerae Cascade-TniQ complex unveiled a new paradigm in biology, demonstrating that CRISPR-associated proteins can direct DNA transposition. Despite the tremendous potential of "knocking-in" genes at desired sites, the mechanisms underlying DNA binding and transposition remain elusive. In this system, a conformational change of the Cas8 protein is essential for DNA binding, yet how it occurs is unclear. Here, structural modeling and free energy simulations reconstruct the Cas8 helical bundle and reveal an open-closed conformational change that is key for the complex's function. We show that when Cascade-TniQ binds RNA, the Cas8 bundle changes conformation mediated by the interaction with the Cas7.1 protein. This interaction promotes the bundle's transition toward the ope

SUBMITTER: Patel AC 

PROVIDER: S-EPMC12002280 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature