Fundamental Characteristics of AAA+ Protein Family Structure and Function

Miller, Justin M.; Enemark, Eric J.

doi:10.1155/2016/9294307

Cited by 92 publications

(100 citation statements)

References 118 publications

(222 reference statements)

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“…An overview of the different AAA + protein clades. All AAA + proteins form higher order homo-or hetero-oligomers that form asymmetric ring structures with heterogeneous nucleotide occupancies (28)(29)(30)(31)(32)(33). All monomers contain a nucleotide binding site for ATP, and additional insertions (highlighted in orange on the monomer structures) that aid their unique functions.…”

Section: Figurementioning

confidence: 99%

Bacterial Enhancer Binding Proteins—AAA+ Proteins in Transcription Activation

Gao

Danson

et al. 2020

Biomolecules

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Bacterial enhancer-binding proteins (bEBPs) are specialised transcriptional activators. bEBPs are hexameric AAA+ ATPases and use ATPase activities to remodel RNA polymerase (RNAP) complexes that contain the major variant sigma factor, σ54 to convert the initial closed complex to the transcription competent open complex. Earlier crystal structures of AAA+ domains alone have led to proposals of how nucleotide-bound states are sensed and propagated to substrate interactions. Recently, the structure of the AAA+ domain of a bEBP bound to RNAP-σ54-promoter DNA was revealed. Together with structures of the closed complex, an intermediate state where DNA is partially loaded into the RNAP cleft and the open promoter complex, a mechanistic understanding of how bEBPs use ATP to activate transcription can now be proposed. This review summarises current structural models and the emerging understanding of how this special class of AAA+ proteins utilises ATPase activities to allow σ54-dependent transcription initiation.

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Section: Figurementioning

confidence: 99%

Bacterial Enhancer Binding Proteins—AAA+ Proteins in Transcription Activation

Gao

Danson

et al. 2020

Biomolecules

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“…We found that the mutation P504L was located at the second AAA domain (between residues 486 to 575). AAA family of domains have conserved modules which bring together active site elements of adjacent subunits for ATP hydrolysis [6]. This is required for generation of mechanical force for translocation of substrate which in case of SARS-CoV2 helicase should be the RNA duplex that needs to unwind for the replication to initiate or progress.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, a mutation in this domain could have modulatory function on RNA replication by possibly modulating either the efficiency of ATP hydrolysis or the dynamics/speed of RNA unwinding. In a report by Wei et al, it was shown that a P to L mutation in the ATPase p97 showed enhanced ATPase activity [6] and desensitized this protein against its inhibitors. In another study by Lin et al it was demonstrated that a mutation from P to L in the reverse transcriptase domain of Hepatitis B virus (HBV) increased replication competency of the enzyme [8].…”

Section: Resultsmentioning

confidence: 99%

Two mutations P/L and Y/C in SARS-CoV-2 helicase domain exist together and influence helicase RNA binding

Begum

Banerjee

Tripathi

et al. 2020

Preprint

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RNA helicases play pivotal role in RNA replication by catalysing the unwinding of complex RNA duplex structures into single strands in ATP/NTP dependent manner. SARS coronavirus 2 (SARS-CoV-2) is a single stranded positive sense RNA virus belonging to the family Coronaviridae. The viral RNA encodes non structural protein Nsp13 or the viral helicase protein that helps the viral RNA dependent RNA polymerase (RdRp) to execute RNA replication by unwinding the RNA duplexes. In this study we identified a novel mutation at position 541of the helicase where the tyrosine (Y) got substituted with cytosine (C). We found that Y541C is a destabilizing mutation increasing the molecular flexibility and leading to decreased affinity of helicase binding with RNA. Earlier we had reported a mutation P504L in the helicase protein for which had not performed RNA binding study. Here we report that P504L mutation leads to increased affinity of helicase RNA interaction. So, both these mutations have opposite effects on RNA binding. Moreover, we found a significant fraction of isolate population where both P504L and Y541C mutations were coexisting.

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“…While a conserved sequence motif of GxxGxGK[T/S] (P-loop/Walker A motif) coordinates the α- and β-phosphates in both ATPases and GTPases (Wittinghofer, 2016), the remaining catalytic machinery, specificity determinants, and charge-compensating elements vary from enzyme to enzyme. AAA+ proteins contain four additional sequence motifs – Walker B, Sensor I, Sensor II, and second region of homology (SRH) – that contribute to ATP binding and hydrolysis along with the conserved P-loop/Walker A motif (Erzberger and Berger, 2006; Miller and Enemark, 2016). The Walker B motif (D[D/E]xx) stabilizes an essential magnesium cofactor and acts in concert with a polar residue in the Sensor I motif to orient the catalytic water for nucleophilic attack on the γ-phosphate.…”

Section: Resultsmentioning

confidence: 99%

Structural asymmetry governs the assembly and GTPase activity of McrBC restriction complexes

Niu

Suzuki

Hosford

et al. 2020

Preprint

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13McrBC complexes are motor-driven nucleases functioning in bacterial self-defense by cleaving 14 foreign DNA. The GTP-specific AAA+ protein McrB powers translocation along DNA and its 15 hydrolysis activity is stimulated by its partner nuclease McrC. Here, we report cryo-EM 16 structures of Thermococcus gammatolerans McrB and McrBC, and E. coli McrBC. The McrB 17 hexamers, containing the necessary catalytic machinery for basal GTP hydrolysis, are 18 intrinsically asymmetric. This asymmetry directs McrC binding so that it engages a single active 19 site, where it then uses an arginine/lysine-mediated hydrogen-bonding network to reposition the 20 asparagine in the McrB signature motif for optimal catalytic function. While the two McrBC 21 complexes use different DNA-binding domains, these contribute to the same general GTP-22 recognition mechanism employed by all G proteins. Asymmetry also induces distinct inter-23 subunit interactions around the ring, suggesting a coordinated and directional GTP-hydrolysis 24 cycle. Our data provide novel insights into the conserved molecular mechanisms governing 25 McrB family AAA+ motors. upon research conducted at NE-CAT beamlines (24-ID-C and 24-ID-E) under the general user

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Fundamental Characteristics of AAA+ Protein Family Structure and Function

Cited by 92 publications

References 118 publications

Bacterial Enhancer Binding Proteins—AAA+ Proteins in Transcription Activation

Bacterial Enhancer Binding Proteins—AAA+ Proteins in Transcription Activation

Two mutations P/L and Y/C in SARS-CoV-2 helicase domain exist together and influence helicase RNA binding

Structural asymmetry governs the assembly and GTPase activity of McrBC restriction complexes

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