The motor domains of ABC-transporters

Oswald, Christine; Holland, I. B.; Schmitt, Lutz

doi:10.1007/s00210-005-0031-4

Cited by 131 publications

(102 citation statements)

References 88 publications

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“…The two composite ATP-binding sites are formed by residues from both NBDs. In this model, ATP hydrolysis is followed by dissociation of the dimers, and the energy that drives the conformational changes for substrate transport (power stroke) is provided by the dimer association/dissociation (7,9,10,12,16,18,21). 2) Constant contact model.…”

Section: Abcmentioning

confidence: 99%

Kinetics of the Association/Dissociation Cycle of an ATP-binding Cassette Nucleotide-binding Domain

Zoghbi

Fuson

Sutton

et al. 2012

Journal of Biological Chemistry

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Background: ATP induces dimerization of the nucleotide-binding domains (NBD) of ATP-binding cassette proteins, followed by ATP hydrolysis and dimer dissociation. Results: The rate of dimerization induced by MgATP is faster than previously thought. Conclusion: During the hydrolysis cycle, there is a dynamic equilibrium where neither monomers nor dimers are favored. Significance: Knowledge of the mechanism of hydrolysis by NBDs will help us understand the function of ATP-binding cassette proteins.

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Section: Abcmentioning

confidence: 99%

Kinetics of the Association/Dissociation Cycle of an ATP-binding Cassette Nucleotide-binding Domain

Zoghbi

Fuson

Sutton

et al. 2012

Journal of Biological Chemistry

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“…In a number of bacterial ABC proteins, the NBDs and TMDs are expressed as separate proteins, which associate to form a functional unit. The analysis of the solved structures of dimeric NBDs of MJ0796, HlyB, MalK, and Rad50, as well as the studies on the structures of "complete" ABC transporters, which also contain the TMDs (BtuCD and MsbA), demonstrated that the two NDBs dimerize in a head-to-tail orientation and form two composite ATP-binding sites/catalytic sites [118]. In these dimeric arrangements, the Walker A of one NBD and the ABC signature motif of the other NBD are involved in the formation of an ATP-binding site.…”

Section: Catalytic Cycle Of Mrp1mentioning

confidence: 99%

“…The structures of ATP-bound NBD dimers show that the conserved second Gly residue in the ABC signature motif interacts with the oxygen of the gamma-phosphate of the ATP, bound to the Walker motif of the opposite subunit [118]. Substitution of these glycines for aspartic acids in either NBDs of MRP1 eliminates transport activity, but the mutants are still capable of forming the transition-state complex [157].…”

Section: Catalytic Cycle Of Mrp1mentioning

confidence: 99%

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

Bakos

Homolya

2006

Pflugers Arch - Eur J Physiol

148

104

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MRP1 (ABCC1) is a peculiar member of the ABC transporter superfamily for several aspects. This protein has an unusually broad substrate specificity and is capable of transporting not only a wide variety of neutral hydrophobic compounds, like the MDR1/P-glycoprotein, but also facilitating the extrusion of numerous glutathione, glucuronate, and sulfate conjugates. The transport mechanism of MRP1 is also complex; a composite substratebinding site permits both cooperativity and competition between various substrates. This versatility and the ubiquitous tissue distribution make this transporter suitable for contributing to various physiological functions, including defense against xenobiotics and endogenous toxic metabolites, leukotriene-mediated inflammatory responses, as well as protection from the toxic effect of oxidative stress. In this paper, we give an overview of the considerable amount of knowledge which has accumulated since the discovery of MRP1 in 1992. We place special emphasis on the structural features essential for function, our recent understanding of the transport mechanism, and the numerous assignments of this transporter.

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“…3,26,and 27) have provided many valuable insights into the function of the ABC cassettes. In the ATP-bound state, NBDs form a composite dimer (28 -30).…”

Section: Atp-binding Cassette (Abc)mentioning

confidence: 99%

Engineering ATPase Activity in the Isolated ABC Cassette of Human TAP1

Ernst

Koch

Horn

et al. 2006

Journal of Biological Chemistry

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The human transporter associated with antigen processing (TAP) translocates antigenic peptides from the cytosol into the endoplasmic reticulum lumen. The functional unit of TAP is a heterodimer composed of the TAP1 and TAP2 subunits, both of which are members of the ABC-transporter family. ABC-transporters are ATP-dependent pumps, channels, or receptors that are composed of four modules: two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Although the TMDs are rather divergent in sequence, the NBDs are conserved with respect to structure and function. Interestingly, the NBD of TAP1 contains mutations at amino acid positions that have been proposed to be essential for catalytic activity. Instead of a glutamate, proposed to act as a general base, TAP1 contains an aspartate and a glutamine instead of the conserved histidine, which has been suggested to act as the linchpin. We used this degeneration to evaluate the individual contribution of these two amino acids to the ATPase activity of the engineered TAP1-NBD mutants. Based on our results a catalytic hierarchy of these two fundamental amino acids in ATP hydrolysis of the mutated TAP1 motor domain was deduced. ATP-binding cassette (ABC)3 -transporters form a large superfamily of primary transmembrane proteins (1), which ultimately use the energy of ATP hydrolysis to translocate their substrate or allocrite (2), the term we prefer to distinguish the transported substrate from ATP. Found in all three kingdoms of life, ABC-transporters contain certain sequence motifs such as the Walker A and B motifs, the C-loop (ABC signature motif), and the D-loop (3, 4). These sequences serve as diagnostic tools to identify ABC-transporters. Furthermore, all members of this family show a modular architecture composed of two nucleotide-binding domains (NBDs), which contain all the conserved sequence motifs, and two transmembrane domains (TMDs). In archea and eubacteria, these four modules are generally encoded on separate genes, whereas they are fused on a single polypeptide chain ("full-size" transporter) in eukarya. Additionally, fusions of one NBD and one TMD, which are called "half-size" transporters, are found in all organisms. The functional unit of these systems would be a homo-or heterodimer of two half-size transporters. Examples of the latter are hemolysin B (HlyB) from Escherichia coli (5) and the human transporter associated with antigen processing (TAP) (6).Human TAP, located in the membrane of the endoplasmic reticulum (ER), is a key component of major histocompatibility complex class I-mediated adaptive immunity (7). The functional TAP complex is a heterodimer composed of TAP1 and TAP2, both of which comprise a TMD-NBD fusion. It is now firmly established that the allocrites of TAP, antigenic peptides, which are generated in the cytosol by proteasomal degradation (8, 9), are transported in an ATP-dependent manner across the ER membrane for subsequent loading of major histocompatibility complex class I molecules (10). After passing the ER quali...

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The motor domains of ABC-transporters

Cited by 131 publications

References 88 publications

Kinetics of the Association/Dissociation Cycle of an ATP-binding Cassette Nucleotide-binding Domain

Kinetics of the Association/Dissociation Cycle of an ATP-binding Cassette Nucleotide-binding Domain

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

Engineering ATPase Activity in the Isolated ABC Cassette of Human TAP1

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