ABC transporters: the power to change

Structural and mechanistic insights into prokaryotic energy-coupling factor transporters

“…Four different structural classes have been discovered, which probably have different mechanisms of substrate translocation (see the figure): type I importers (which are exemplified by the maltose transporter MalEFGK 2 from Escherichia coli [57][58][59][60][61] ; Protein Data Bank (PDB) accession 2R6G); type II importers (exemplified by vitamin B 12 transporter BtuC 2 D 2 F from E. coli [62][63][64] ; PDB accession 4FI3); exporters (such as multidrug and peptide transporters [65][66][67] , exemplified by the drug exporter TM287/288) from Thermotoga maritima; PDB accession 3QF4); and ECF transporters (such as ECF-FolT from Lactobacillus brevis for folate transport 21 ; PDB accession 4HUQ). Type I and II importers and energy-coupling factor (ECF) transporters are only found in prokaryotes, whereas exporters are found in all kingdoms of life 28 .…”

“…In all ABC transporters, ATP binding and hydrolysis takes place at the interface between the ATPase subunits (EcfA and EcfAʹ in ECF transporters), where two ATP binding sites are located 28,51 FIG. 3d).…”

“…Although the amino acid sequences of EcfT proteins are highly diverse, they can be identified by two short conserved Ala-Arg-Gly motifs (see below) 27 . The two ATPases of the ECF module belong to the large family of ATPases (also known as nucleotide-binding domains (NBDs)) that are found in ATP-binding cassette (ABC) transporters 28 ; thus, ECF transporters form a branch of this large superfamily of transporters…”

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

“…[6][7][8] Each MetN ABC subunit can be further divided into two subdomains 9 ; the nucleotide binding domain (NBD; residues 1-245) and a C-terminal domain (C2; residues 265-343) connected by a linker spanning residues 246-264. The MetI subunits contain five transmembrane (TM) helices that define a conserved core present in the Type I family of ABC importers, 10,11 including the previously solved structures of the ModBC molybdate 12 and MalFGK 2 maltose 13 transporters. In addition to the transporter subunits, importers require a periplasmic binding protein (MetQ for the MetNI system) to deliver the proper substrate.…”

“…14,15 The mechanism of ABC transporters is generally interpreted in terms of an alternating access model 16,17 where substrate translocation is coupled to the ATP dependent interconversion of inward and outward facing conformations. 11,12,18 The binding and hydrolysis of ATP requires association of the NBDs to form a closed dimer, with the nucleotide binding site positioned at the dimer interface. [19][20][21][22] In the conformation competent for ATP hydrolysis, the nucleotides are sandwiched between the conserved P-loop and ABC signature motifs from opposing ABC subunits.…”