Fungal PDR transporters: Phylogeny, topology, motifs and function.
The overexpression of pleiotropic drug resistance (PDR) efflux pumps of the ATP-binding cassette (ABC) transporter superfamily frequently correlates with multidrug resistance. Phylogenetic analysis of 349 full-size ( approximately 160kDa) PDR proteins (Pdrps) from 55 fungal species, including major fungal pathogens, identified nine separate protein clusters (A-G, H1a/H1b and H2). Fungal, plant and human ABCG-family Pdrps possess a nucleotide-binding domain [NBD] and a transmembrane domain [TMD] in a family-defining 'reverse' ABC transporter topology [NBD-TMD] that is duplicated [NBD-TMD](2) in full-size fungal and plant Pdrps. Although full-size Pdrps have similar halves indicating early gene duplication/fusion, they show asymmetry of their NBDs and extracellular loops (ELs). Members of cluster F are most symmetric and may be closely related to the evolutionary ancestor of Pdrps. Unique structural elements are predicted, new PDR-specific motifs identified, and the significance of these and other structural features discussed.
Lamping
Erwin
E
Department of Oral Sciences, University of Otago, Dunedin, New Zealand.
Baret
Philippe V
PV
Holmes
Ann R
AR
Monk
Brian C
BC
Goffeau
Andre
A
Cannon
Richard D
RD
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D020816:Amino Acid Motifs; D000935:Antifungal Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000737:chemistry; D025141:Drug Resistance, Fungal / Q000235:genetics / Q000502:physiology*; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D005658:Fungi / Q000145:classification* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010802:Phylogeny
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D004268:DNA-Binding Proteins; D005656:Fungal Proteins