8PJB

Cryo-EM structure of MLE in complex with UUC RNA and ADP

Summary for 8PJB

• Entry DOI: 10.2210/pdb8pjb/pdb
• EMDB information: 17703
• Descriptor: Dosage compensation regulator, RNA (5'-R(P*CP*UP*CP*UP*UP*UP*CP*UP*U)-3'), ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: rna helicase, rna binding protein
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 134411.58

Authors

Jagtap, P.K.A.,Hennig, J. (deposition date: 2023-06-23, release date: 2023-11-01, Last modification date: 2025-07-02)

Primary citation

Jagtap, P.K.A.,Muller, M.,Kiss, A.E.,Thomae, A.W.,Lapouge, K.,Beck, M.,Becker, P.B.,Hennig, J.
Structural basis of RNA-induced autoregulation of the DExH-type RNA helicase maleless.
Mol.Cell, 83:4318-4333.e10, 2023

PubMed Abstract: RNA unwinding by DExH-type helicases underlies most RNA metabolism and function. It remains unresolved if and how the basic unwinding reaction of helicases is regulated by auxiliary domains. We explored the interplay between the RecA and auxiliary domains of the RNA helicase maleless (MLE) from Drosophila using structural and functional studies. We discovered that MLE exists in a dsRNA-bound open conformation and that the auxiliary dsRBD2 domain aligns the substrate RNA with the accessible helicase tunnel. In an ATP-dependent manner, dsRBD2 associates with the helicase module, leading to tunnel closure around ssRNA. Furthermore, our structures provide a rationale for blunt-ended dsRNA unwinding and 3'-5' translocation by MLE. Structure-based MLE mutations confirm the functional relevance of our model for RNA unwinding. Our findings contribute to our understanding of the fundamental mechanics of auxiliary domains in DExH helicase MLE, which serves as a model for its human ortholog and potential therapeutic target, DHX9/RHA.

PubMed: 37989319
DOI: 10.1016/j.molcel.2023.10.026

Experimental method

ELECTRON MICROSCOPY (3.62 Å)