Solution and Crystal Structures of mRNA Exporter Dbp5p and Its Interaction with Nucleotides

Fan, Jun; Chen, Zhihong; Zhang, Jingfeng; Noble, Christian G.; Zhou, Zhi-Hong; Song, Haiwei; Yang, Daiwen

doi:10.1016/j.jmb.2009.03.004

Cited by 48 publications

(44 citation statements)

References 42 publications

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“…All of the described structures of DEAD box proteins in the presence of RNA have revealed a highly conserved mode of RNA binding [13][14][15][16][17][18] . The bound RNA is characteristically bent into a conformation that differs from that seen for nucleic acids bound to most other SF2 and SF1 helicases 14 .…”

Section: Structures Of Dead Box Rna Helicasesmentioning

confidence: 99%

“…Whether these two steps correspond to discrete structural changes is not yet clear. Structures of ATP analogues and RNA bound together captured highly similar conformations of different DEAD box proteins [13][14][15][16]18,44 . It is thought that these structures correspond to the conformation that is acquired after the second step of ATP binding and represent the state following the strand separation event 13 .…”

Section: Atp Ground Statementioning

confidence: 99%

“…It is thought that these structures correspond to the conformation that is acquired after the second step of ATP binding and represent the state following the strand separation event 13 . In this conform ation, the two RecA-like domains are in a closed conformation [13][14][15][16]18,44 and thus complete and organize the ATP-binding and RNA-binding sites (FIG. 2).…”

Section: Atp Ground Statementioning

confidence: 99%

“…Nup159 blocks the RNA binding site 17 . The crystal structure of Dbp5 bound to RNA and ATP is based on Fan et al 18 . H C, carboxy-terminal helicase core domain; H N, amino-terminal helicase core domain.…”

Section: Nuclear Specklesmentioning

confidence: 99%

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From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

956

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: Structures Of Dead Box Rna Helicasesmentioning

confidence: 99%

Section: Atp Ground Statementioning

confidence: 99%

Section: Atp Ground Statementioning

confidence: 99%

Section: Nuclear Specklesmentioning

confidence: 99%

See 2 more Smart Citations

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

956

1,069

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“…When overall RNA affinities are determined, nucleotide-dependent substrate binding properties of the core will thus be masked by the nucleotideindependent high RNA affinity of the flanking domain, and it is crucial to dissect the individual contributions. Recent evidence suggests that additional domains can also influence nucleotide binding (Collins et al, 2009;Fan et al, 2009;Napetschnig et al, 2009;von Moeller et al, 2009), see also the section on 'modulation of the helicase core activity by interacting partners and flanking domains'.…”

Section: Interaction Of Dead Box Proteins With Adenine Nucleotides Anmentioning

confidence: 99%

The mechanism of ATP-dependent RNA unwinding by DEAD box proteins

Hilbert

Karow²,

Klostermeier³

2009

BCHM

140

171

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DEAD box proteins catalyze the ATP-dependent unwinding of double-stranded RNA (dsRNA). In addition, they facilitate protein displacement and remodeling of RNA or RNA/protein complexes. Their hallmark feature is local destabilization of RNA duplexes. Here, we summarize current data on the DEAD box protein mechanism and present a model for RNA unwinding that integrates recent data on the effect of ATP analogs and mutations on DEAD box protein activity. DEAD box proteins share a conserved helicase core with two flexibly linked RecAlike domains that contain all helicase signature motifs. Variable flanking regions contribute to substrate binding and modulate activity. In the presence of ATP and RNA, the helicase core adopts a compact, closed conformation with extensive interdomain contacts and high affinity for RNA. In the closed conformation, the RecA-like domains form a catalytic site for ATP hydrolysis and a continuous RNA binding site. A kink in the backbone of the bound RNA locally destabilizes the duplex. Rearrangement of this initial complex generates a hydrolysisand unwinding-competent state. From this complex, the first RNA strand can dissociate. After ATP hydrolysis and phosphate release, the DEAD box protein returns to a low-affinity state for RNA. Dissociation of the second RNA strand and reopening of the cleft in the helicase core allow for further catalytic cycles.

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Rearranging RNA structures at 75°C? toward the molecular mechanism and physiological function of the thermus thermophilus DEAD‐box helicase hera

Klostermeier

2013

Biopolymers

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DEAD-box helicases catalyze the ATP-dependent destabilization of RNA duplexes. Hera is a DEAD-box helicase from Thermus thermophilus that consists of a helicase core, followed by a C-terminal extension comprising a dimerization domain and an RNA-binding domain. The combined structural information on individual Hera domains provides a molecular model of the Hera dimer. The modular architecture with flexible connections between individual domains affords different relative orientations of the RBD relative to the Hera helicase core, and of the two helicase cores within the dimer. Presumably, domain movements are intimately linked to RNA binding, to the interplay of the RBD and the helicase core, and to RNA unwinding, and may impact on the functional cooperation of the two helicase cores in RNA unwinding. The in vivo function of Hera is unknown. The Hera RBD recognizes two distinct elements in the RNA substrate, a single-stranded and a structured region. The helicase core then unwinds an adjacent RNA duplex in an ATP-dependent reaction. Overall, this mode of action is reminiscent of DEAD-box proteins that act as general RNA chaperones. This review summarizes the current knowledge on Hera structure and function, and discusses a possible role of Hera in the Thermus thermophilus cold-shock response.

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Solution and Crystal Structures of mRNA Exporter Dbp5p and Its Interaction with Nucleotides

Cited by 48 publications

References 42 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

The mechanism of ATP-dependent RNA unwinding by DEAD box proteins

Rearranging RNA structures at 75°C? toward the molecular mechanism and physiological function of the thermus thermophilus DEAD‐box helicase hera

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