Article Dans Une Revue Journal of Biological Chemistry Année : 2023

Nonstructural N- and C-tails of Dbp2 confer the protein full helicase activities

Résumé

Human DDX5 and its yeast ortholog Dbp2 are ATP-dependent RNA helicases that play a keyrole in normal cell processes, cancer development and viral infection. The crystal structure ofthe RecA1-like domain of DDX5 is available, but the global structure of DDX5/Dbp2subfamily proteins remains to be elucidated. Here, we report the first X-ray crystal structuresof the Dbp2 helicase core alone and in complex with adenosine diphosphate nucleotide (ADP)at 3.22 Å and 3.05 Å resolutions, respectively. The structures of the ADP-bound post-hydrolysisstate and apo-state demonstrate the conformational changes that occur when the nucleotides arereleased. Our results showed that the helicase core of Dbp2 shifted between open and closedconformation in solution, but the unwinding activity was hindered when the helicase core wasrestricted to a single conformation. A small-angle X-ray scattering (SAXS) experiment showedthat the disordered amino- (N-) and carboxy- (C-) tails are flexible in solution. Truncationmutations confirmed that the N- and C-tails were critical for the nucleic acid binding, ATPase,and unwinding activities, with the C-tail being exclusively responsible for the annealing activity.Furthermore, we labeled the terminal tails to observe the conformational changes between thedisordered tails and the helicase core upon binding nucleic acid substrates. Specifically, wefound that the nonstructural N- and C-tails bind to RNA substrates and tether them to thehelicase core domain, thereby conferring full helicase activities to the Dbp2 protein. Thisdistinct structural characteristic provides new insight into the mechanism of DEAD-box RNAhelicases.

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hal-04019832 , version 1 (09-07-2025)

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Qin-Xia Song, Na-Nv Liu, Zhao-Xia Liu, Ying-Zi Zhang, Stephane Rety, et al.. Nonstructural N- and C-tails of Dbp2 confer the protein full helicase activities. Journal of Biological Chemistry, In press, 299 (5), pp.104592. ⟨10.1016/j.jbc.2023.104592⟩. ⟨hal-04019832⟩
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