On the Evolution of Specificity in Members of the Yeast Amino Acid Transporter Family as Parts of Specific Metabolic Pathways

Abstract

In the recent years, molecular modeling and substrate docking, coupled with biochemical and genetic analyses have identified the substrate-binding residues of several amino acid transporters of the yeast amino acid transporter (YAT) family. These consist of (a) residues conserved across YATs that interact with the invariable part of amino acid substrates and (b) variable residues that interact with the side chain of the amino acid substrate and thus define specificity. Secondary structure sequence alignments showed that the positions of these residues are conserved across YATs and could thus be used to predict the specificity of YATs. Here, we discuss the potential of combining molecular modeling and structural alignments with intra-species phylogenetic comparisons of transporters, in order to predict the function of uncharacterized members of the family. We additionally define some orphan branches which include transporters with potentially novel, and to be characterized specificities. In addition, we discuss the particular case of the highly specific l-proline transporter, PrnB, of Aspergillus nidulans, whose gene is part of a cluster of genes required for the utilization of proline as a carbon and/or nitrogen source. This clustering correlates with transcriptional regulation of these genes, potentially leading to the efficient coordination of the uptake of externally provided l-Pro via PrnB and its enzymatic degradation in the cell.

Amino acid permeases in Cryptococcus neoformans are required for high temperature growth and virulence; and are regulated by Ras signaling

“…Gournas et al (2018) reported that a limited number of amino acid residues located at five transmembrane segments of yeast APC transporters is required for amino acid binding and specificity [69]. The most relevant residues are at transmembrane segment 1 (TM1), with two glycines, which are invariable in 14 aligned sequences of the yeast APC superfamily.…”

Function and Regulation of Acid Resistance Antiporters

“…Several yeast amino acid transporters (YATs) that feature various substrate specificity ranges and affinities help yeast cells to survive in various environments (André 2018;Gournas et al 2016Gournas et al , 2018. Most of these YAT proteins are proton symporters that belong to the APC superfamily (Gournas et al 2016).…”

Identification of an Acidic Amino Acid Permease Involved in d-Aspartate Uptake in the Yeast Cryptococcus humicola

“…In fungi, amino acids are imported into cells by amino acid permeases (Aaps) located in the plasma membrane. Most yeast Aaps belong to the yeast amino acid transporter (YAT) family, a group of proteins in the amino acid - polyamine-organocation (APC) superfamily [ 17 ]. Aap homologs of the APC superfamily are found in fungi as well as animals, plants, and bacteria [ 18 ].…”

“…The typical YAT possesses 12 transmembrane regions (TMs) and functions as a symporter through proton-driven secondary active transport [ 19 , 20 ]. In the yeast Saccharomyces cerevisiae , 19 Aaps have been identified [ 17 ]. The yeast Aaps have different substrate specificities.…”