ATP Modulates Subunit-Subunit Interactions in an ATP-binding Cassette Transporter (MalFGK2) Determined by Site-directed Chemical Cross-linking

Hunke, Sabine; Mourez, Michaël; Jéhanno, Muguette; Dassa, Elie; Schneider, Erwin

doi:10.1074/jbc.275.20.15526

Cited by 80 publications

(90 citation statements)

References 39 publications

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“…This choice was further supported by the analysis of biochemical data. In this dimer, slight structural rearrangements placed the Q-loop in a position, which matched the biochemical data derived from S. typhimurium MalK crosslinking studies (Hunke et al 2000). The dimer interface of the MalK structure is formed by apolar residues (22), many of them being aromatic, as well as by polar residues (29).…”

Section: Dimeric Arrangement -Problems and Solutionssupporting

confidence: 59%

The motor domains of ABC-transporters

Oswald

Holland

Schmitt

2006

Naunyn Schmied Arch Pharmacol

133

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The transport of substrates across a cellular membrane is a vitally important biological function essential for cell survival. ATP-binding cassette (ABC) transporters constitute one of the largest subfamilies of membrane proteins, accomplishing this task. Mutations in genes encoding for ABC transporters cause different diseases, for example, Adrenoleukodystrophy, Stargardt disease or Cystic Fibrosis. Furthermore, some ABC transporters are responsible for multidrug resistance, presenting a major obstacle in modern cancer chemotherapy. In order to translocate the enormous variety of substrates, ranging from ions, nutrients, small peptides to large toxins, different ABC-transporters utilize the energy gained from ATP binding and hydrolysis. The ATP binding cassette, also called the motor domain of ABC transporters, is highly conserved among all ABC transporters. The ability to purify this domain rather easily presents a perfect possibility to investigate the mechanism of ATP hydrolysis, thus providing us with a detailed picture of this process. Recently, many crystal structures of the ATP-binding domain and the full-length structures of two ABC transporters have been solved. Combining these structural data, we have now the opportunity to analyze the hydrolysis event on a molecular level. This review provides an overview of the structural investigations of the ATPbinding domains, highlighting molecular changes upon ATP binding and hydrolysis.

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Section: Dimeric Arrangement -Problems and Solutionssupporting

confidence: 59%

The motor domains of ABC-transporters

Oswald

Holland

Schmitt

2006

Naunyn Schmied Arch Pharmacol

133

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“…7). Because the EAA loop is in close contact with the ATPase subunits (13) membrane domain C-terminal to the amphipathic helices and the EAA loop is predicted.…”

Section: Resultsmentioning

confidence: 99%

Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Hebbeln

Rodionov

Alfandega

et al. 2007

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

132

190

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BioMNY proteins are considered to constitute tripartite biotin transporters in prokaryotes. Recent comparative genomic and experimental analyses pointed to the similarity of BioMN to homologous modules of prokaryotic transporters mediating uptake of metals, amino acids, and vitamins. These systems resemble ATP-binding cassette-containing transporters and include typical ATPases (e.g., BioM). Absence of extracytoplasmic solute-binding proteins among the members of this group, however, is a distinctive feature. Genome context analyses uncovered that only onethird of the widespread bioY genes are linked to bioMN. Many bioY genes are located at loci encoding biotin biosynthesis, and others are unlinked to biotin metabolic or transport genes. Heterologous expression of the bioMNY operon and of the single bioY of the ␣-proteobacterium Rhodobacter capsulatus conferred biotin-transport activity on recombinant Escherichia coli cells. Kinetic analyses identified BioY as a high-capacity transporter that was converted into a high-affinity system in the presence of BioMN. BioMNY- Biotin is synthesized by many bacteria, certain archaea, fungi, and plants (reviewed in ref. 2). Several metabolic routes seem to exist for the synthesis of the intermediate pimeloyl-CoA, which then is converted into biotin in a four-step path encoded by the universal genes bioF, bioA, bioD, and bioB (3, 4). In plants, the pathway is distributed between the cytosol and the mitochondria. At least the final step, catalyzed by biotin synthase, occurs in mitochondria. This enzyme, a member of the radical SAM enzyme family, inserts a sulfur atom into dethiobiotin in a complex reaction that is linked to mitochondrial iron/sulfur metabolism (2).Biotin uptake has been analyzed in eukaryotes. In mammalian cells, the vitamin is transported across the plasma membrane by a sodium-dependent multivitamin transporter and, at least in certain tissues, by monocarboxylate transporter 1 (1). In the naturally biotin-auxotrophic yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, biotin uptake is mediated by unrelated proton symporters (5). Surprisingly little is known on the mechanisms behind biotin transport into prokaryotic cells, and multiple systems seem to exist. Active transport was observed for Escherichia coli K-12 Ͼ30 years ago (6). Despite extensive experimental work, knowledge of the complete genome sequence, and assignment of the biotin-transport locus to the 75-min genomic region, the gene(s) for the biotin transporter has not yet been identified. Recent studies by Walker and Altman (7) suggest that this system in E. coli and related Gram-negative bacteria not only transports the small vitamin, but in addition facilitates the uptake of biotinylated peptides with chain lengths up to 31 amino acid residues.In 2002, Entcheva et al. (8) reported that mutations in bioM and bioN lead to reduced biotin uptake in Sinorhizobium meliloti. Because the products of these two genes share distinct similarity with CbiO and CbiQ, which are components of prokary...

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Section: Discussionmentioning

confidence: 99%

“…When a Cys substitution is introduced to Ala-85 in the Q loop region, cross-linked MalK dimer is observed only upon addition of ATP (33). The failure of ADP to induce cross-linking suggests that ATP, but not ADP, induces closure of the NBDs in MalFGK 2 (33). Photocleavage experiments using vanadate as a transition state analogue indicate that ATP hydrolysis occurs in the closed dimer (34), and the solvent accessibility of a fluorescent probe covalently attached to an amino acid in the Walker A motif is reduced in the catalytic transition state as compared with the resting state (35), consistent with the closure of the interface between the NBDs.…”

Section: Discussionmentioning

confidence: 99%