Chimeras of the ABC drug transporter Cdr1p reveal functional indispensability of transmembrane domains and nucleotide-binding domains, but transmembrane segment 12 is replaceable with the corresponding homologous region of the non-drug transporter Cdr3p

Microbiology
Preeti SainiRajendra Prasad

Abstract

The molecular basis of the broad substrate recognition and the transport of substrates by Cdr1p, a major drug efflux protein of Candida albicans, is not well understood. To investigate the role of transmembrane domains and nucleotide-binding domains (NBDs) of Cdr1p in drug transport, two sets of protein chimeras were constructed: one set between homologous regions of Cdr1p and the non-drug transporter Cdr3p, and another set consisting of Cdr1p variants comprising either two N- or two C-terminal NBDs of Cdr1p. The replacement of either the N- or the C-terminal half of Cdr1p by the homologous segments of Cdr3p resulted in non-functional recombinant strains expressing chimeric proteins. The results suggest that the chimeric protein could not reach the plasma membrane, probably because of misfolding and subsequent cellular trafficking problems, or the rapid degradation of the chimeras. As an exception, the replacement of transmembrane segment 12 (TMS12) of Cdr1p by the corresponding region of Cdr3p resulted in a functional chimera which displayed unaltered affinity for all the tested substrates. The variant protein comprising either two N-terminal or two C-terminal NBDs of Cdr1p also resulted in non-functional recombinant strains. ...Continue Reading

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Citations

Feb 19, 2009·Antimicrobial Agents and Chemotherapy·Sarah TsaoMartine Raymond
Jun 19, 2012·Annual Review of Microbiology·Rajendra Prasad, Andre Goffeau
Feb 9, 2012·Journal of Amino Acids·Rajendra PrasadManpreet Kaur Rawal
Sep 16, 2014·Frontiers in Pharmacology·Rajendra Prasad, Manpreet K Rawal
Jul 9, 2016·Glycoconjugate Journal·Roberta Salinas-MarínIván Martínez-Duncker
Sep 27, 2015·Eukaryotic Cell·Rajendra PrasadSanjiveeni Dhamgaye
Sep 29, 2019·Research in Microbiology·Alexis MorenoPierre Falson

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