Structural Basis of DEAH/RHA Helicase Activity

Michael C Chen,Adrian R Ferré-D’Amaré

doi:10.3390/cryst7080253

Michael C Chen, Adrian R Ferré-D’Amaré

Open Access

https://doi.org/10.3390/cryst7080253

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Abstract

DEAH/RHA helicases are members of a large group of proteins collectively termed DExH-box, which also include Ski2-like and NS3/NPH-II helicases. By binding and remodeling DNA and RNA, DEAH/RHA helicases play critical roles in many cellular processes ranging from transcription and splicing to ribosome biogenesis, innate immunity and stress granule formation. While numerous crystal structures of other DExH-box proteins helicases have been reported, no structures of DEAH/RHA helicases bound to nucleic acid substrates have been available until the recent co-crystal structures of the maleless (MLE) and Prp43p bound to RNA. This review examines how these new structures provide a starting point to understand how DEAH/RHA helicases bind to, translocate on, and unwind nucleic acid substrates.

Highlights

DEAH/RHA helicases belong to a group of SF2 helicases collectively called DExH-box proteins, which consist of the following families: Ski2-like and NS3/NPH-II [1,2,3]
The co-crystal structures of MLE (MLE-rU-TR) [23] and Prp43p (Prp43p-rU-GR) [44,45] bound to RNA substrates in the transition and ground states, respectively show that, like other SF2 helicases, DEAH/RHA helicases interact with their nucleic acid substrate via the helicase core region typically through three motifs in the RecA1 domain at the 30 -end and four motifs in the RecA2 domain at the
This mutation resulted in impaired unwinding capabilities, which demonstrates that the observed CTD rotation is crucial to DEAH/RHA helicase activity

Summary

Introduction

DEAH/RHA helicases belong to a group of SF2 helicases collectively called DExH-box proteins, which consist of the following families: Ski2-like and NS3/NPH-II [1,2,3]. The co-crystal structures of MLE (MLE-rU-TR) [23] and Prp43p (Prp43p-rU-GR) [44,45] bound to RNA substrates in the transition and ground states, respectively show that, like other SF2 helicases, DEAH/RHA helicases interact with their nucleic acid substrate via the helicase core region typically through three motifs in the RecA1 domain at the 30 -end and four motifs in the RecA2 domain at the. In Ski2-like helicases the HP motif directly separates the two strands of a nucleic acid duplex [32,60,61], whereas in DEAH/RHA helicases the HP motif appears to be out of position to perform such a role due to extensive protein-protein contacts with the OB sub-domain In both MLE and Prp43p, the HP motif sterically occludes the path of the nucleic acid substrate resulting in an abrupt flip of the nucleotide bases so that the bases are pointing away from the HP motif (Figure 3b,c). The HP motif may play a role in substrate unwinding by providing strain directly 30 to any nucleic acid secondary structure

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