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Faculty Sponsor

Dr. George S. Mourad

Department/Program

Department of Biology

University Affiliation

Indiana University – Purdue University Fort Wayne

Abstract

The Nucleobase-Ascorbate Transporter (NAT) family is found in every major taxa with over 2000 putative members. Despite the structural similarities amongst putative members, the less than 20 characterized NATs have distinct transport profiles. Microbial, plant, and non-primate mammalian NATs are specific for uracil, xanthine, and/or uric acid; whereas, mammalian NATs transport vitamin C. These hugely different specificities make NATs candidates for the rational design of antifungal and antibacterial drugs, as human and microbial NATs transport different substrates. The Arabidopsis thaliana genome contains 12 putative members of the NAT family, whose functions have previously eluded discovery. Radiolabeled uptake studies of AtNAT1 through AtNAT8 heterologously expressed in Saccharomyces cerevisiae deficient in native nucleobase transport revealed each AtNAT, except AtNAT3, to share the canonical plant NAT specificity profile of xanthine and uric acid. Conversely, a novel substrate specificity of xanthine, adenine, guanine, and hypoxanthine was revealed for AtNAT3. In planta radiolabeled uptake studies utilizing an AtNAT3 insertion knockout mutant confirmed xanthine transport. This work functionally characterizes 8 more NATs and identifies the novel specificity profile of AtNAT3, despite high sequence similarity, greatly adding to the structure-function information available for this ubiquitous family.

Disciplines

Biology | Life Sciences

Functional Characterization of the Arabidopsis Nucleobase-Ascorbate Transporter Family (NAT) Reveals Distinct Transport Profiles and Novel Substrate Specificity

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