A key structural domain of the Candida albicans Mdr1 protein

The Biochemical Journal
Ajeet MandalRajendra Prasad

Abstract

A major multidrug transporter, MDR1 (multidrug resistance 1), a member of the MFS (major facilitator superfamily), invariably contributes to an increased efflux of commonly used azoles and thus corroborates their direct involvement in MDR in Candida albicans. The Mdr1 protein has two transmembrane domains, each comprising six transmembrane helices, interconnected with extracellular loops and ICLs (intracellular loops). The introduction of deletions and insertions through mutagenesis was used to address the role of the largest interdomain ICL3 of the MDR1 protein. Most of the progressive deletants, when overexpressed, eliminated the drug resistance. Notably, restoration of the length of the ICL3 by insertional mutagenesis did not restore the functionality of the protein. Interestingly, most of the insertion and deletion variants of ICL3 became amenable to trypsinization, yielding peptide fragments. The homology model of the Mdr1 protein showed that the molecular surface-charge distribution was perturbed in most of the ICL3 mutant variants. Taken together, these results provide the first evidence that the CCL (central cytoplasmic loop) of the fungal MFS transporter of the DHA1 (drug/proton antiporter) family is critical for the f...Continue Reading

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Citations

Feb 14, 2013·Trends in Biochemical Sciences·Nieng Yan
Aug 4, 2015·Protein Science : a Publication of the Protein Society·Xuejun C ZhangDaohua Jiang
Sep 16, 2014·Frontiers in Pharmacology·Rajendra Prasad, Manpreet K Rawal
May 18, 2016·FEMS Yeast Research·Archana K RedhuRajendra Prasad
Sep 19, 2018·Drug Discoveries & Therapeutics·Siddhartha KumarAntresh Kumar
Jun 7, 2019·BMC Complementary and Alternative Medicine·Neelam KumariAntresh Kumar
Jan 18, 2018·Journal of Molecular Biology·Archana Kumari RedhuRajendra Prasad

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