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

Strohmeier, Julian; Hertel, Ines; Diederichsen, Ulf; Rudolph, M.G.; Klostermeier, Dagmar

doi:10.1515/bc.2011.034

Cited by 9 publications

(12 citation statements)

References 55 publications

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“…2). Many residues of the ATP-binding site form a complex network of interactions 12,13 , which makes it a challenge to generate DEAD box protein mutants that are deficient in ATP hydrolysis but intact in ATP binding.…”

Section: Structures Of Dead Box Rna Helicasesmentioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

988

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%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

988

1,069

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“…Notably, the residues in the ATP binding and hydrolysis site form a highly complex interaction network [33,34]. This interconnection complicates the introduction of mutations that prevent ATP hydrolysis without affecting ATP binding.…”

Section: Structural Characteristics Of Dead-box Helicasesmentioning

confidence: 99%

“…DEAD-box proteins are generally specific for adenosine triphosphates for driving duplex unwinding and for RNA-stimulated hydrolysis of the triphosphate [33,34]. This specificity is mostly conferred by the Q-motif, which establishes specific contacts to adenine-specific functional groups [35].…”

Section: Structural Characteristics Of Dead-box Helicasesmentioning

confidence: 99%

DEAD-box helicases as integrators of RNA, nucleotide and protein binding

Putnam

Jankowsky

2013

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

192

207

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DEAD-box helicases perform diverse cellular functions in virtually all steps of RNA metabolism from Bacteria to Humans. Although DEAD-box helicases share a highly conserved core domain, the enzymes catalyze a wide range of biochemical reactions. In addition to the well established RNA unwinding and corresponding ATPase activities, DEAD-box helicases promote duplex formation and displace proteins from RNA. They can also function as assembly platforms for larger ribonucleoprotein complexes, and as metabolite sensors. This review aims to provide a perspective on the diverse biochemical features of DEAD-box helicases and connections to structural information. We discuss these data in the context of a model that views the enzymes as integrators of RNA, nucleotide, and protein binding.

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“…A very recent study of the RNA helicase Hera examined the effect of the glutamic acid substituted for the invariant glutamine within the Q motif. This work suggested that the Q motif is responsible for sensing the nucleotide state of the helicase and establishing a stable interaction of the Walker A box (P-loop) with other helicase motifs, and this stabilization is required for catalytic competence (13).…”

mentioning

confidence: 99%

The Q Motif of Fanconi Anemia Group J Protein (FANCJ) DNA Helicase Regulates Its Dimerization, DNA Binding, and DNA Repair Function

Sommers

Loiland

et al. 2012

Journal of Biological Chemistry

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Background:The conserved Q motif of RNA/DNA helicases has been structurally implicated in nucleotide binding; however, its biochemical functions are less certain. Results: Mutagenesis of the Q motif in FANCJ DNA helicase perturbs dimerization, DNA binding, and catalytic function. Conclusion: The Q motif is essential for FANCJ enzymatic activity and DNA repair. Significance: The FANCJ Q motif is important for its biochemical and cellular functions.

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

Cited by 9 publications

References 55 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

DEAD-box helicases as integrators of RNA, nucleotide and protein binding

The Q Motif of Fanconi Anemia Group J Protein (FANCJ) DNA Helicase Regulates Its Dimerization, DNA Binding, and DNA Repair Function

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