8B9I

Cryo-EM structure of MLE in complex with ADP:AlF4 and UUC RNA

8B9I の概要

• エントリーDOI: 10.2210/pdb8b9i/pdb
• EMDBエントリー: 15932
• 分子名称: Dosage compensation regulator, RNA (5'-R(P*CP*CP*UP*CP*UP*UP*UP*CP*UP*UP*U)-3'), ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: rna helicase, drosophila dosage compensation, rna binding protein
• 由来する生物種: Drosophila melanogaster (fruit fly); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 134643.66

構造登録者

Jagtap, P.K.A.,Hennig, J. (登録日: 2022-10-06, 公開日: 2023-10-18, 最終更新日: 2024-05-01)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.95 Å)