InterPro domain: IPR000515

ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein (mostly in eukaryotes and bacterial exporters) or on two different ones (mostly bacterial importers) [ 1 ]. In importers, the TMD displays a distinctive signature, the EAA motif, a 20 amino acid conserved sequence located about 100 residues from the C terminus. The motif is hydrophilic and has been found to reside in a cytoplasmic loop located between the penultimate and the antepenultimate transmembrane segment in all proteins with a known topology [ 2 ]. It appears to play an important role in ensuring the correct assembly of the prokaryotic ABC transport complex [ 3 ] and constituting an interaction site with the so-called helical domain of the ABC module [ 4 , 5 ].

This entry recognises ABC transmembrane domains where the TMD is on a separate protein, such as the D-methionine transport system permease protein MetI. The crystal structure of the high-affinity Escherichia coli MetNI methionine uptake transporter has been solved. Each MetI subunit is organised around a core of five transmembrane helices that correspond to a subset of the helices observed in the larger membrane-spanning subunits of the molybdate (ModBC) and maltose (MalFGK) ABC transporters, which contain six helices [ 6 , 7 ].

1. Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. J. Mol. Evol. 48, 22-41
2. Bacterial binding protein-dependent permeases: characterization of distinctive signatures for functionally related integral cytoplasmic membrane proteins. Mol. Microbiol. 12, 993-1004
3. ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains. FEMS Microbiol. Rev. 22, 1-20
4. ATP modulates subunit-subunit interactions in an ATP-binding cassette transporter (MalFGK2) determined by site-directed chemical cross-linking. J. Biol. Chem. 275, 15526-34
5. Subunit interactions in ABC transporters: a conserved sequence in hydrophobic membrane proteins of periplasmic permeases defines an important site of interaction with the ATPase subunits. EMBO J. 16, 3066-77
6. The high-affinity E. coli methionine ABC transporter: structure and allosteric regulation. Science 321, 250-3
7. The MsmX ATPase plays a crucial role in pectin mobilization by Bacillus subtilis. PLoS One 12, e0189483