9MW6
Cryo-EM structure of ancestral Dicer helicase bound to 27-bp dsRNA
Summary for 9MW6
| Entry DOI | 10.2210/pdb9mw6/pdb |
| EMDB information | 48678 |
| Descriptor | AncD1D2, RNA (27-MER) (3 entities in total) |
| Functional Keywords | rna helicase, dsrbm, antiviral protein-rna complex, antiviral protein/rna |
| Biological source | synthetic construct More |
| Total number of polymer chains | 3 |
| Total formula weight | 92710.90 |
| Authors | Aderounmu, A.M.,Consalvo, C.D.,Shen, P.S.,Bass, B.L. (deposition date: 2025-01-16, release date: 2025-03-12) |
| Primary citation | Aderounmu, A.M.,Maus-Conn, J.,Consalvo, C.D.,Shen, P.S.,Bass, B.L. Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins. Biorxiv, 2025 Cited by PubMed Abstract: 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 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. PubMed: 39990435DOI: 10.1101/2025.02.15.638221 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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