Rebuilt AAA + motors reveal operating principles for ATP-fuelled machines

Martin, Andreas; Baker, Tania A.; Sauer, Robert T.

doi:10.1038/nature04031

Cited by 356 publications

(439 citation statements)

References 37 publications

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“…ClpS, a 12-kDa adaptor protein specific for the prokaryotic ClpAP protease (27,28,30), contains a region of sequelogy to a conserved sequence of the much larger UBR1 and other E3 Ub ligases (N-recognins) of the eukaryotic N-end rule pathway (12,45). ClpS is the N-recognin of the E. coli N-end rule pathway, where it binds to the Nd p residues Leu, Phe, Trp, or Tyr (31).…”

Section: Identical Specificities Of Ate1 and Atel1 May Be The Results Ofmentioning

confidence: 99%

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Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen

Graciet

Hu²,

Piatkov³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

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The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Primary destabilizing N-terminal residues (Nd p ) are recognized directly by the targeting machinery. The recognition of secondary destabilizing N-terminal residues (Nd s ) is preceded by conjugation of an Nd p residue to Nd s of a polypeptide substrate. In eukaryotes, ATE1 -encoded arginyl-transferases (R D,E,C* -transferases) conjugate Arg (R), an Nd p residue, to Nd s residues Asp (D), Glu (E), or oxidized Cys residue (C*). Ubiquitin ligases recognize the N-terminal Arg of a substrate and target the (ubiquitylated) substrate to the proteasome. In prokaryotes such as Escherichia coli , Nd p residues Leu (L) or Phe (F) are conjugated, by the aat -encoded Leu/Phe-transferase (L/F K,R -transferase), to N-terminal Arg or Lys, which are Nd s in prokaryotes but Nd p in eukaryotes. In prokaryotes, substrates bearing the Nd p residues Leu, Phe, Trp, or Tyr are degraded by the proteasome-like ClpAP protease. Despite enzymological similarities between eukaryotic R D,E,C* -transferases and prokaryotic L/F K,R -transferases, there is no significant sequelogy (sequence similarity) between them. We identified an aminoacyl-transferase, termed Bpt, in the human pathogen Vibrio vulnificus . Although it is a sequelog of eukaryotic R D,E,C* -transferases, this prokaryotic transferase exhibits a “hybrid” specificity, conjugating Nd p Leu to Nd s Asp or Glu. Another aminoacyl-transferase, termed ATEL1, of the eukaryotic pathogen Plasmodium falciparum , is a sequelog of prokaryotic L/F K,R -transferases (Aat), but has the specificity of eukaryotic R D,E,C* -transferases (ATE1). Phylogenetic analysis suggests that the substrate specificity of R-transferases arose by two distinct routes during the evolution of eukaryotes.

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Section: Identical Specificities Of Ate1 and Atel1 May Be The Results Ofmentioning

confidence: 99%

“…1 A and B) (7,25,26). Reporter substrates bearing the Nd p residues Leu, Phe, Trp (W), or Tyr (Y) are targeted for degradation by ClpAP (27)(28)(29)(30), one of several proteasome-like proteases in E. coli. ClpS, a 12-kDa adaptor protein specific for ClpAP, is an essential component of the E. coli N-end rule pathway, where it functions as the N-recognin (Fig.…”

mentioning

confidence: 99%

Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen

Graciet

Hu²,

Piatkov³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

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Section: Hydrolysis Sequence and Timingmentioning

confidence: 99%

“…Alternative models include a probabilistic hydrolysis mechanism as suggested for the bacterial unfoldase ClpX, a hexameric AAA+ peptidetranslocating machine [79 ]. ClpX does not require six active subunits to translocate a peptide for degradation, inconsistent with both fully concerted as well as strictly sequential mechanisms [79 ]. A concerted hydrolysis mechanism has been described for Tag, but because of the many sequence, structural, and functional similarities, we expect that all SF3 helicases, including Tag, to coordinate DNA and operate by a sequential hydrolysis escort mechanism described above for E1.…”

Section: Hydrolysis Sequence and Timingmentioning

confidence: 99%

“…In the case of T7gp4, DNA-dependent ATPase activity has been shown to require an active catalytic base (E343) at all six subunit interfaces [66 ], but some inactive arginine fingers are permitted [87]. The most direct studies of a multisubunit machine's tolerance to individual ATP site disruption involve the bacterial unfoldase ClpX [79 ]. These studies demonstrate that ClpX will continue to function with inactive ATP sites and that the relative arrangement of the inactive sites is an important determinant of activity.…”

Section: Tolerance To Atp Site Disruptionmentioning

confidence: 99%

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On helicases and other motor proteins

Enemark

Joshua‐Tor

2008

Current Opinion in Structural Biology

190

238

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Helicases are molecular machines that utilize energy derived from ATP hydrolysis to move along nucleic acids and to separate base-paired nucleotides. The movement of the helicase can also be described as a stationary helicase that pumps nucleic acid. Recent structural data for the hexameric E1 helicase of papillomavirus in complex with single-stranded DNA and MgADP has provided a detailed atomic and mechanistic picture of its ATP-driven DNA translocation. The structural and mechanistic features of this helicase are compared with the hexameric helicase prototypes T7gp4 and SV40 T-antigen. The ATP-binding site architectures of these proteins are structurally similar to the sites of other prototypical ATP-driven motors such as F1-ATPase, suggesting related roles for the individual site residues in the ATPase activity. IntroductionHelicases are essential enzymes that unwind duplex DNA, RNA, or DNA-RNA hybrids. This unwinding is driven by consumption of input energy that is harnessed to separate base-paired oligonucleotides and also to maintain a unidirectional advancement of the helicase upon the nucleic acid substrate. This translocation can alternatively be described as an immobile helicase pumping nucleic acid. The energy for these transformations is derived from the hydrolysis of nucleotide triphosphate (NTP). Helicases can be depicted as an internal combustion engine with each individual NTPase site serving as one cylinder. Each individual cylinder follows a defined series of events: injection (ATP binding), compression (optimally positioning the site for hydrolysis), combustion (ATP hydrolysis/work generation), and exhaust (ADP and phosphate release). In a helicase, the individual combustion cylinders coordinate these actions to carry out the repetitive mechanical operation of prying open base pairs and/or actively translocating with respect to the nucleic acid substrate. Many other molecular motors utilize similar engines to carry out multiple diverse functions such as translocation of peptides in the case of ClpX, movement along cellular structures in the case of dyenin, and rotation about an axle as in F 1 -ATPase.Based upon conserved sequence motifs, helicases have been classified into six superfamilies [1,2 ]. An extensive review of these superfamilies has been provided recently [3 ]. Superfamily 1 (SF1) and superfamily 2 (SF2) helicases are very prevalent, generally monomeric, and participate in several diverse DNA and RNA manipulations. The other helicase superfamilies form hexameric rings (reviewed in [4]), as demonstrated by biochemistry [5][6][7][8] and electron microscopy studies [9][10][11][12][13][14][15][16][17], and often participate at the replication fork. All of these helicases bind and hydrolyze NTP at the interface between two recA-like domains. The binding site consists of a Walker A (P-loop) and a Walker B motif from the first domain and other elements such as an arginine finger from the other domain. The SF1 and SF2 helicases contain two recAlike domains coupled by a short linker, and t...

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