Structure of the Exon Junction Core Complex with a Trapped DEAD-Box ATPase Bound to RNA

Andersen, Christian Brix Folsted; Ballut, Lionel; Johansen, Jesper; Chamieh, Hala; Nielsen, Klaus; Oliveira, Cristiano L. P.; Pedersen, Jan Skov; Séraphin, Bertrand; Hir, Hervé Le; Andersen, G.R.

doi:10.1126/science.1131981

Cited by 391 publications

(533 citation statements)

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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%

“…Crystal structure analysis shows that eIF4AIII binds RNA in an ATP-dependent fashion and serves as a platform for the assembly of the EJC core factors 15,16 (FIG. 3c).…”

Section: Atp Ground Statementioning

confidence: 99%

“…However, structural studies indicate that ATP is bound in the EJC 15,16 . Biochemical data, in conjunction with a structure containing an ATP transition state analogue (ADP-aluminium fluoride (ADP-AlF x )), have shown that hydrolysis can occur within the complex without loss of the high affinity for RNA 44 .…”

Section: Atp Ground Statementioning

confidence: 99%

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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: Structures Of Dead Box Rna Helicasesmentioning

confidence: 99%

Section: Atp Ground Statementioning

confidence: 99%

Section: Atp Ground Statementioning

confidence: 99%

“…Crystal structure analysis shows that eIF4AIII binds RNA in an ATP-dependent fashion and serves as a platform for the assembly of the EJC core factors 15,16 (FIG. 3c).…”

Section: Atp Ground Statementioning

confidence: 99%