Domainal evolution of a prokaryotic DNA repair protein and its relationship to active-transport proteins

Doolittle, R.F.; Johnson, M. S.; Husain, Intisar; Houten, Ben Van; Thomas, David C.; Sancar, Aziz

doi:10.1038/323451a0

Cited by 188 publications

(106 citation statements)

References 17 publications

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“…The likelihood that such useful units would be distributed into many proteins with a specified functiondl need was an early hypothesis by Gilbert [49] and Blake [50, 511, who postulated that exons coded for units of secondary structure, and that the same exon could be distributed into many different genes. While there is insufficient data to relate the various motifs described here with exons in their genes, it has been stated that Walker A and B segments should be independently folding domains [52], which is consistent with considering them as protein modules. The benefits of such modular architecture have been more specifically described for enzymes, where the functional benefit of using two modules for a ligand-binding pocket were considered [47,481.…”

Section: Motifs and Modulesmentioning

confidence: 68%

The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide‐binding sites

Traut

1994

European Journal of Biochemistry

354

216

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From an analysis of current data on 16 protein structures with defined nucleotide-binding sites consensus motifs were determined for the peptide segments that form such nucleotide-binding sites. This was done by using the actual residues shown to contact ligands in the different protein structures, plus an additional 50 sequences for various kinases. Three peptide segments are commonly required to form the binding site for ATP or GTP. Binding motif Kinase-1 a is found in almost all sequences examined, and functions in binding the phosphates of the ligand. Variant versions, comparable to Kinase-1 a, are found in a subset of proteins and appear to be related to unique functions of those enzymes. Motif Kinase-2 contains the conserved aspartate that coordinates the metal ion on Mg-ATP. Motif Kinase-3 occurs in at least four versions, and functions in binding the purine base or the pentose. Two protein structures show ATP-binding at a separate regulatory site, formed by the motifs Regulatory-1 and Regulatory-2. Structures for adenylate kinase and guanylate kinase show three different sequence motifs that form the binding site for a nucleoside monophosphate (NMP). NMP-I and NMP-2 bind to the pentose and phosphate of the bound ligand. NMP-I is found in almost all the kinases that phosphorylate AMP, CMP, GMP, dTMP, or UMP. NMP-3a is found in kinases for AMP, GMP, and UMP, while NMP-3b binds only GMP. For the binding of NTPs, three distinct types of nucleotide-binding fold structures have been described. Each structure is associated with a particular function (e.g. transfer of the y-phosphate, or of the adenylate to an acceptor) and also with a particular spatial arrangement of the three Kinase segments evident in the linear sequence for the protein.With the rapid proliferation of DNA sequences in the last decade, the finding that a few consensus sequences might generally correspond to ATP-binding sites was immediately useful. In 1982 Walker et al. deduced from a search of available sequences for ATP-binding proteins that one, or both, of two sequence motifs appeared in nine proteins, with four proteins having both sequences [l]. Since both of these motifs occurred in porcine adenylate kinase, at positions corresponding to the proposed nucleotide-bindmg site in the crystal structure [2], the association of these sequences with actual ATP-bindmg appeared to be established. Although adenylate kinase uses ATP to phosphorylate AMP, the crystal structure then available had some ambiguity as to whether the Walker A site or the Walker B site bound ATP or AMP; the appearance of these motif sequences in other ATP-binding proteins favored the former nucleotide site. Since this original paper also found only a Walker B sequence in phosphofructokinase [l], an easy interpretation was that either

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Section: Motifs and Modulesmentioning

confidence: 68%

The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide‐binding sites

Traut

1994

European Journal of Biochemistry

354

216

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“…One possible explanation for the observed stoichiometry is that ATP hydrolysis has become uncoupled from histidine transport. By analogy to the uncoupling observed in the FoF1 (22) (25,26), and understanding the molecular biology of these proteins is an increasingly important goal in fields as distinct as oncology (8), cell division, and protein secretion (26). Based on work reported here, we suggest that each example in this class couples ATP hydrolysis to some transport event and that the histidine permease serves as a useful model for the entire group.…”

Section: Resultsmentioning

confidence: 99%

Reconstitution of a bacterial periplasmic permease in proteoliposomes and demonstration of ATP hydrolysis concomitant with transport.

Bishop

Agbayani

Ambudkar

et al. 1989

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

154

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The histidine periplasmic permease of Salmonela typhimuium has been partially purified and reconstituted into proteoliposomes. In this in vitro preparation, transport activity is completely dependent on the presence of all four permease proteins (HisJ, HisQ, HisM, and HisP) and on internal ATP. The reconstituted system shows initial rates of transport that are comparable to those obtained with right-side-out membrane vesicles and it establishes a 100-fold concentration gradient for histidine. have been hypothesized to be involved in the coupling ofATP to substrate transport (6, 7). Interestingly, proteins homologous to this family have been discovered also in eukaryotic organisms where they are also involved in transport-related processes, such as in the multidrug-resistance excretion mechanism (MDR) and in the transport and deposit of the Drosophila eye pigment (8,9).Our studies utilize as a model system the well-characterized histidine permease of Salmonella typhimurium (10), which is composed of the histidine-binding protein, HisJ, two hydrophobic integral membrane proteins, HisQ and HisM, and the nucleotide-binding membrane protein, HisP. Data obtained using intact cells implicated ATP as the energy source, and it was shown incontrovertibly that the electrochemical gradient is not involved in energization (3). In vitro studies were also initiated in order to approach the question of the proximal energy source from a biochemical point of view and to advance our understanding of the molecular mechanism of action of these permeases. With an in vitro system that utilizes right-side-out membrane vesicles to which the histidine-binding protein is added externally (11,12), additional evidence was obtained that energization is derived from the ATP generated from the electrochemical gradient via the proton-conducting FoF1 ATPase; it was also shown that the liganded binding protein is the true substrate in transport, interacting with the membrane complex with a Km of 65 j.M (12). A second in vitro system, which consists of inside-out membrane vesicles containing entrapped histidine-binding protein and energized by externally added ATP, but not by a nonhydrolyzable analog of ATP, also supplied evidence that ATP is the proximal energy source and that its hydrolysis is necessary (13). However, both above systems are unsatisfactory for further biochemical studies, since the only pure protein utilized is HisJ, the others being still embedded in membrane vesicles. We now describe a third system, reconstituted proteoliposomes.Protedliposome reconstitution of periplasmic permeases has not been previously attempted, presumably because of the complex multicomponent nature of these systems and of the uncertainty as to their mechanism of energization. In addition, the methodology for reconstituting bacterial permeases in general was not available until fairly recently (14-17). Armed with the availability of the overproduction of our permease membrane proteins, with the presumption that ATP is the energy source, and with t...

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“…UvrA includes the requisite sequence motifs (see below) and is clearly a member of the ABC family with, uniquely, three ABC domains (Doolittle et al, 1986). UvrA is also unique in that it is the only ABC protein characterized to date with a role unrelated to membrane transport.…”

Section: The Excision Nuclease Uvramentioning

confidence: 99%

“…The vast majority of ABC proteins are associated with the transport of substrates across biological membranes, although the DNA excision repair enzyme UvrA provides a notable exception (Doolittle et al, 1986). Many human ABC transporters are associated with disease states (e.g.…”

Section: Introductionmentioning

confidence: 99%

The Escherichia coli ATP‐binding cassette (ABC) proteins

Linton

Higgins

1998

Molecular Microbiology

390

278

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SummaryThe recent completion of the Escherichia coli genome sequence (Blattner et al., 1997) has permitted an analysis of the complement of genomically encoded ATPbinding cassette (ABC) proteins. A total of 79 ABC proteins makes this the largest paralogous family of proteins in E. coli. These 79 proteins include 97 ABC domains (as some proteins include more than one ABC domain) and are components of 69 independent functional systems (as many systems involve more than one ABC domain). The ABC domains are often, but not exclusively, the energy-generating domains of multicomponent membrane-bound transporters. Thus, 57 of the 69 systems are ABC transporters, of which 44 are periplasmic-binding protein-dependent uptake systems and 13 are presumed exporters. The genes encoding these ABC transporters occupy almost 5% of the genome. Of the 12 systems that are not obviously transport related, the function of only one, the excision repair protein UvrA, is known. A phylogenetic analysis suggests that the majority of ABC proteins can be assigned to 10 subfamilies. Together with statistical and, importantly, biological evidence, this analysis provides insight into the evolution and function of the ABC proteins.

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Domainal evolution of a prokaryotic DNA repair protein and its relationship to active-transport proteins

Cited by 188 publications

References 17 publications

The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide‐binding sites

The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide‐binding sites

Reconstitution of a bacterial periplasmic permease in proteoliposomes and demonstration of ATP hydrolysis concomitant with transport.

The Escherichia coli ATP‐binding cassette (ABC) proteins

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