Crystallographic structure of the amino terminal domain of yeast initiation factor 4A, a representative DEAD-box RNA helicase

Johnson, Eric R.; McKay, David

doi:10.1017/s1355838299991410

Cited by 74 publications

(76 citation statements)

References 33 publications

(27 reference statements)

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“…The P-loop of BstDEAD, however, is atypical. It adopts a closed conformation, similar to that first described in the N-terminal domain structure of eIF4A (Johnson and McKay 1999) but not seen in any other RNA or DNA helicase, with or without ATP. Although no biological relevance has thus far been ascribed to the unique closed conformation, it appears as though the closed P-loop of BstDEAD would sterically inhibit ATP binding.…”

Section: Conserved Motifssupporting

confidence: 64%

“…In addition to interactions with the Q-motif described above, coordinated interactions with the DEAD motif are important for formation of the ATP binding cleft. The conserved residues in the Q-motif, P-loop, and DEAD motif of BstDEAD-NT are positioned almost identically to those in the structure of eIF4A (Johnson and McKay 1999). With the exception of the closed P-loop conformation, the conserved motifs in BstDEAD also superimpose on those of mjDEAD (Story et al 2001) and PcrA (Subramanya et al 1996).…”

Section: Conserved Motifsmentioning

confidence: 87%

“…Although no biological relevance has thus far been ascribed to the unique closed conformation, it appears as though the closed P-loop of BstDEAD would sterically inhibit ATP binding. In Figure 5, the closed P-loop conformations of BstDEAD and eIF4a (Johnson and McKay 1999) are shown compared with the open conformations of mjDEAD (Story et al 2001) and PcrA (Velankar et al 1999) with a bound ATP analog. The closed P-loop conformation of eIF4A results from swiveling around Gly70 and Ala65 (Johnson and McKay 1999).…”

Section: Conserved Motifsmentioning

confidence: 99%

“…In Figure 5, the closed P-loop conformations of BstDEAD and eIF4a (Johnson and McKay 1999) are shown compared with the open conformations of mjDEAD (Story et al 2001) and PcrA (Velankar et al 1999) with a bound ATP analog. The closed P-loop conformation of eIF4A results from swiveling around Gly70 and Ala65 (Johnson and McKay 1999). Gly53 in BstDEAD is analogous to Gly70 in eIF4A as the "pivot" around which the P-loop rotates.…”

Section: Conserved Motifsmentioning

confidence: 99%

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Crystal structure of the BstDEAD N-terminal domain: A novel DEAD protein from Bacillus stearothermophilus

Carmel

Matthews²

2003

RNA

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Most cellular processes requiring RNA structure rearrangement necessitate the action of Asp-Glu-Ala-Asp (DEAD) proteins. Members of the family, named originally for the conserved DEAD amino acid sequence, are thought to disrupt RNA structure and facilitate its rearrangement by unwinding short stretches of duplex RNA. BstDEAD is a novel 436 amino acid representative of the DEAD protein family from Bacillus stearothermophilus that contains all eight conserved motifs found in DEAD proteins and is homologous with other members of the family. Here, we describe the 1.85 Å resolution structure of the N-terminal domain (residues 1-211) of BstDEAD (BstDEAD-NT). Similar to the corresponding domains of related helicases, BstDEAD-NT adopts a parallel ␣/␤ structure with RecA-like topology. In general, the conserved motifs superimpose on closely related DEAD proteins and on more distantly related helicases such as RecA. This affirms the current belief that the core helicase domains, responsible for mechanistic activity, are structurally similar in DEAD proteins. In contrast, however, the so-called Walker A P-loop, which binds the ␤-and ␥-phosphates of ATP, adopts a rarely seen "closed" conformation that would sterically block ATP binding. The closed conformation may be indicative of a general regulatory feature among DEAD proteins (and RNA helicases) that differs from that used by DNA helicases. BstDEAD also contains a unique extension of ∼ 60 residues at the C terminus that is highly basic, suggesting that it might bind nucleic acids and, in so doing, confer specificity to the helicase activity of the core region.

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Section: Conserved Motifssupporting

confidence: 64%

Section: Conserved Motifsmentioning

confidence: 87%

Section: Conserved Motifsmentioning

confidence: 99%

Section: Conserved Motifsmentioning

confidence: 99%

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Crystal structure of the BstDEAD N-terminal domain: A novel DEAD protein from Bacillus stearothermophilus

Carmel

Matthews²

2003

RNA

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“…Linden and D. Klostermeier, unpublished). As the phosphate groups in nucleotides do not provide additional binding energy, it could be concluded that the energy from hydrogen bonds of the phosphate part to the P-loop is transformed into conformational changes of the DEAD and SAT motifs toward a closure of the helicase inter-domain cleft in the ATP state (Yao et al, 1997;Kim et al, 1998;Johnson and McKay, 1999;Caruthers et al, 2000;Linden et al, 2008). In TthDEAD_Q28E, the hydrogen bonding network connecting the Q-motif, the P-loop, the DEAD-box and the SAT motif is maintained and these motifs have shifted in a concerted fashion when compared to the structures of the DEAD-box proteins Vasa, DDX19 and DBP5 in complex with RNA and ADPNP (Sengoku et al, 2006;Collins et al, 2009;von Moeller et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Changing nucleotide specificity of the DEAD-box helicase Hera abrogates communication between the Q-motif and the P-loop

Strohmeier¹,

Hertel²,

Diederichsen³

et al. 2011

Biological Chemistry

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DEAD-box proteins disrupt or remodel RNA and protein/ RNA complexes at the expense of ATP. The catalytic core is composed of two flexibly connected RecA-like domains. The N-terminal domain contains most of the motifs involved in nucleotide binding and serves as a minimalistic model for helicase/nucleotide interactions. A single conserved glutamine in the so-called Q-motif has been suggested as a conformational sensor for the nucleotide state. To reprogram the Thermus thermophilus RNA helicase Hera for use of oxo-ATP instead of ATP and to investigate the sensor function of the Q-motif, we analyzed helicase activity of Hera Q28E. Crystal structures of the Hera N-terminal domain Q28E mutant (TthDEAD_Q28E) in apo-and ligand-bound forms show that Q28E does change specificity from adenine to 8-oxoadenine. However, significant structural changes accompany the Q28E mutation, which prevent the P-loop from adopting its catalytically active conformation and explain the lack of helicase activity of Hera_Q28E with either ATP or 8-oxo-ATP as energy sources. 8-Oxo-adenosine, 8-oxo-AMP, and 8-oxo-ADP weakly bind to TthDEAD_Q28E but in noncanonical modes. These results indicate that the Q-motif not only senses the nucleotide state of the helicase but could also stabilize a catalytically competent conformation of the Ploop and other helicase signature motifs.

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Initiation of Protein Synthesis

Wilson¹,

Hinnebusch²,

Dever³

et al. 2004

Protein Synthesis and Ribosome Structure

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Crystallographic structure of the amino terminal domain of yeast initiation factor 4A, a representative DEAD-box RNA helicase

Cited by 74 publications

References 33 publications

Crystal structure of the BstDEAD N-terminal domain: A novel DEAD protein from Bacillus stearothermophilus

Crystal structure of the BstDEAD N-terminal domain: A novel DEAD protein from Bacillus stearothermophilus

Changing nucleotide specificity of the DEAD-box helicase Hera abrogates communication between the Q-motif and the P-loop

Initiation of Protein Synthesis

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