The DEAD Box Helicase YxiN Maintains a Closed Conformation during ATP Hydrolysis

Aregger, Regula; Klostermeier, Dagmar

doi:10.1021/bi901278p

Cited by 55 publications

(85 citation statements)

References 23 publications

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“…In addition, most of the DEAD box proteins tested to date require only ATP binding for strand separation, and not ATP hydrolysis 39,41,42 . Instead, ATP hydrolysis is necessary for the fast release of DEAD box proteins from the RNA and thus for substrate turnover 40,42,43 .…”

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

983

1,069

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Nearly all aspects of RNA metabolism, from transcription and translation to mRNA decay, involve RNA helicases, which are enzymes that use ATP to bind or remodel RNA and RNA-protein complexes (ribonucleoprotein (RNP) complexes) 1 . RNA helicases are found in all three domains of life, and many viruses also encode one or more of these proteins 2,3 . Together with the structurally related DNA helicases that function in replication, recombination and repair, the RNA helicases are classified into superfamilies and families, based on sequence and structural features 3,4 . DEAD box proteins form the largest helicase family, with 37 members in humans and 26 in Saccharomyces cerevisiae 3 , and are characterized by the presence of an Asp-Glu-Ala-Asp (DEAD) motif.DEAD box helicases have central and, in many cases, essential physiological roles in cellular RNA metabolism 5 (FIG. 1). The proteins generally function as part of larger multicomponent assemblies, such as the spliceosom e or the eukaryotic translation initiation machinery 6 . Mutations and deregulation of several DEAD box proteins have been linked to disease states, including cancer 7 . Although all DEAD box proteins contain a structurally highly conserved core with conserved ATP-binding and RNA-binding sites, different proteins have been associated with diverse and seemingly unrelated functions, including the disassembly of RNPs, chaperoning during RNA folding and even stabil ization of protein complexes on RNA 5,6 . How these highly conserved proteins fulfil such an array of different functions has been a long-standing question.Research has now started to illuminate the molecular basis for this functional diversity. In this Review, we summarize how structural data, together with biochemical and biophysical studies, have revealed unexpected modes by which these proteins function. We also discuss how novel molecular and cell biological approaches have better defined the cellular roles of DEAD box helicases. We outline our current view on common structural and mechan istic themes that have emerged, and on physical models of how these 'unusual' RNA helicases work.Structures of DEAD box RNA helicases A number of structural studies have universally shown that members of the DEAD box family contain a highly conserved helicase core that harbours the binding sites for ATP and RNA 3,4,8 . The core is surrounded by variable auxiliary domains, which are thought to be critical for the diverse functions of these enzymes.Structure of the helicase core. DEAD box proteins belong to helicase superfamily 2 (SF2) 2 . Similarly to all SF2 helicases, DEAD box proteins are built around a highly conserved helicase core of two virtually identical domains that resemble the bacterial recombination protein recombinase A (RecA) 3,4,8 (FIG. 2a,b). Within this helicase core, at least 12 characteristic sequence motifs are located at conserved positions (FIG. 2a,b). Some of these motifs are conserved across the entire SF2 family, whereas others are found only in the DEAD box family 3 ....

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Section: Mitochondrial Rna Editingmentioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

983

1,069

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“…Molecule A:X consists of a 32-nt-long RNA containing helix 92 and a 15-residue single-stranded region 5 ′ of helix 92 annealed to a 9-nt-long RNA strand. This model molecule has been used extensively to investigate DbpA's and YxiN's functional properties Uhlenbeck 2001, 2005;Elles and Uhlenbeck 2008;Theissen et al 2008;Aregger and Klostermeier 2009;Henn et al 2012). Molecule B:X consists of a 32-nt-long DNA-RNA chimera, in which 15 RNA residues 5 ′ of helix 92 have been substituted by DNA residues, annealed to the 9-nt-long RNA.…”

mentioning

confidence: 99%

The DbpA catalytic core unwinds double-helix substrates by directly loading on them

Childs

Gentry

Moore

et al. 2016

RNA

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DbpA is a DEAD-box RNA helicase implicated in the assembly of the large ribosomal subunit. Similar to all the members of the DEAD-box family, the DbpA protein has two N-terminal RecA-like domains, which perform the RNA unwinding. However, unlike other members of this family, the DbpA protein also possesses a structured C-terminal RNA-binding domain that mediates specific tethering of DbpA to hairpin 92 of the Escherichia coli 23S ribosomal RNA. Previous studies using model RNA molecules containing hairpin 92 show that the RNA molecules support the DbpA protein's double-helix unwinding activity, provided that the double helix has a 3 ′ single-stranded region. The 3 ′ single-stranded region was suggested to be the start site of the DbpA protein's catalytic unwinding activity. The data presented here demonstrate that the single-stranded region 3′ of the doublehelix substrate is not required for the DbpA protein's unwinding activity and the DbpA protein unwinds the double-helix substrates by directly loading on them.

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“…Similarly, it is currently unclear how the active state of RIG-I is switched off. ATP hydrolysis and phosphate release will lead to opening of the cleft in the helicase core 4,10,112 and a reduction of its RNA affinity, but the 5′-ppp-end of viral RNAs will remain anchored to the RIG-I CTDs during the ATPase cycle. Rebinding of the CARDs to their interaction site on H2i, and thus the return to the autorepressed state, are only possible once the ubiquitin modification has been cleaved.…”

mentioning

confidence: 99%