9mw7

Cryo-EM structure of ancestral Dicer helicase bound to 27-bp dsRNA in end-bound transition state

spinqualitylabelsall models 9mw7, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9mw7 is a 3 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: ADP, AF3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A fully functional Dicer helicase, present in the modern arthropod, uses energy generated during ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA cleavage required for efficient antiviral defense. However, modern Dicer orthologs exhibit divergent helicase functions that affect their ability to contribute to antiviral defense, and moreover, mechanisms that couple ATP hydrolysis to Dicer helicase movement on dsRNA remain enigmatic. Here, we used biochemical and structural analyses of ancestrally reconstructed Dicer helicases to map evolution of dsRNA binding affinity, ATP hydrolysis and translocation. We found that loss of affinity for dsRNA occurred early in Dicer evolution, coinciding with a decline in translocation activity, despite preservation of ATP hydrolysis activity, exemplified by the ancient deuterostome Dicer. Ancestral nematode Dicer also exhibited significant decline in ATP hydrolysis and translocation, but studies of antiviral activities in the modern nematode C. elegans indicate Dicer retained a role in antiviral defense by recruiting a second helicase. Cryo-EM analyses of an ancient metazoan Dicer allowed capture of multiple helicase states revealing the mechanism that connects each step of ATP hydrolysis to unidirectional movement along dsRNA. Overall, our study rationalizes the diversity in modern Dicer helicases by connecting ancestral functions to observations in extant enzymes. Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins.,Aderounmu AM, Maus-Conn J, Consalvo CD, Shen PS, Bass BL bioRxiv [Preprint]. 2025 Feb 16:2025.02.15.638221. doi: , 10.1101/2025.02.15.638221. PMID:39990435 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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