Fungal PDR transporters: Phylogeny, topology, motifs and function
- 28 February 2010
- journal article
- review article
- Published by Elsevier BV in Fungal Genetics and Biology
- Vol. 47 (2), 127-142
- https://doi.org/10.1016/j.fgb.2009.10.007
Abstract
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.Keywords
Funding Information
- National Institutes of Health (R01DE016885-01)
- the Foundation for Research Science and Technology of New Zealand (UOOX0607)
This publication has 117 references indexed in Scilit:
- Relative Contributions of the Candida albicans ABC Transporters Cdr1p and Cdr2p to Clinical Azole ResistanceAntimicrobial Agents and Chemotherapy, 2009
- Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug BindingScience, 2009
- ABC transporters: the power to changeNature Reviews Molecular Cell Biology, 2009
- Coordinate control of lipid composition and drug transport activities is required for normal multidrug resistance in fungiBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2008
- Mutations Define Cross-talk between the N-terminal Nucleotide-binding Domain and Transmembrane Helix-2 of the Yeast Multidrug Transporter Pdr5Published by Elsevier BV ,2008
- ABC Transporter Cdr1p Contributes More than Cdr2p Does to Fluconazole Efflux in Fluconazole-Resistant Candida albicans Clinical IsolatesAntimicrobial Agents and Chemotherapy, 2008
- A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5Proceedings of the National Academy of Sciences of the United States of America, 2008
- Structure and mechanism of ABC transporter proteinsCurrent Opinion in Structural Biology, 2007
- Genome evolution in yeastsNature, 2004
- Life with 6000 GenesScience, 1996