Structure, Function, and Evolution of Bacterial ATP-Binding Cassette Systems

Abstract

SUMMARY ATP-binding cassette (ABC) systems are universally distributed among living organisms and function in many different aspects of bacterial physiology. ABC transporters are best known for their role in the import of essential nutrients and the export of toxic molecules, but they can also mediate the transport of many other physiological substrates. In a classical transport reaction, two highly conserved ATP-binding domains or subunits couple the binding/hydrolysis of ATP to the translocation of particular substrates across the membrane, through interactions with membrane-spanning domains of the transporter. Variations on this basic theme involve soluble ABC ATP-binding proteins that couple ATP hydrolysis to nontransport processes, such as DNA repair and gene expression regulation. Insights into the structure, function, and mechanism of action of bacterial ABC proteins are reported, based on phylogenetic comparisons as well as classic biochemical and genetic approaches. The availability of an increasing number of high-resolution structures has provided a valuable framework for interpretation of recent studies, and realistic models have been proposed to explain how these fascinating molecular machines use complex dynamic processes to fulfill their numerous biological functions. These advances are also important for elucidating the mechanism of action of eukaryotic ABC proteins, because functional defects in many of them are responsible for severe human inherited diseases.

Inward facing conformations of the MetNI methionine ABC transporter: Implications for the mechanism of transinhibition

“…The structural foundations for this analysis are most advanced for Type I importers, 10 particularly for the maltose MalFGK 2 transporter, [25][26][27][28] and provide an important framework for interpreting the mechanistic significance of the current MetNI structures. Structurally characterized type I importers include MalFGK 2 in outward facing (PDB IDs 2R6G 13 and 3PUY 27 ), pretranslocation (PDB IDs 3PV0 and 3PUZ 27 ), and inward facing (3FH6 36 ) conformations, ModABC in the inward and inward/inhibited conformations (PDB IDs 2ONK 24 and 3D31, 32 respectively), and the CY5 and DM forms of MetNI (PDB IDs 3TUI and 3TUJ, respectively) presented in this work.…”

“…The mechanistic understanding of the transporter cycle is most advanced for Type I importers, particularly the maltose MalFGK 2 importer, where a combination of biochemical, biophysical, and structural studies have provided important insights. [25][26][27][28] These studies have revealed a range of conformational states corresponding to inward and outward facing stabilized with various nucleotides, binding proteins, and mutations.…”

The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

“…Sequence comparison analyses allowed the assignment of UvrA to the ATP binding cassette (ABC) ATPase superfamily (Pfam code: PF09818), whose members are involved in many different cellular functions, ranging from import/export transport across the membranes to non-transport-related phenomena, DNA repair among these (15). …”

Complete genome sequence analysis of the fish pathogen Flavobacterium columnare provides insights into antibiotic resistance and pathogenicity related genes

“…ATP-binding cassette transporters (ABC transporters) utilize the energy of ATP binding and hydrolysis to transport various substrates across cellular membranes. Bacterial ABC transporters and secretion systems are essential in cell viability, virulence, and pathogenicity [33,34]. Seven subclasses of ABC transporter proteins were identified in Pf1 based on different substrates.…”