2.A.96 The Acetate Uptake Transporter (AceTr) Family

YaaH is an E. coli protein of 188aas with 6 putative TMSs. It has homologues in other bacteria, archaea, several fungi and protozoa. S. cerevisiae has 3 paralogues (YCR010c, YDR384c and YNR002c). The homlogue, AcpA, of Aspergillus nidulans, has been shown to be an acetate uptake porter in germinating conidia under conditions when the substrate is not protonated (Robellet et al., 2008). Another homologue of A. nidulans, AlcS, is much more distantly related but is of unknown transport function (Flipphi et al., 2006). In Saccharomyces cerevisiae, the orothologue of AcpA is Ady2 (50% identical).  Evidence indicates that several other homologues are acetate porters (see proteins). Members of this family have the SLC53 fold (Ferrada and Superti-Furga 2022).  There are 10 AceTr homologues in Candida albicans, but only two of them have been shown to be acetate uptake porters. The acetate uptake transporter family motif 'NPAPLGL(M/S)' is essential for substrate uptake (Ribas et al. 2019). The roles of AceTr family porters in Candida Pathogenesis has been reviewed (Alves et al. 2020). Insights into the acetate uptake transporter (AceTr) family by unveiling amino acid residues critical for specificity and activity has appeared (Rendulić et al. 2021). 

SatP (YaaH) of E. coli has been preliminarily identified as a succinate-acetate/proton symporter. Sun et al. 2018 reported the crystal structure of SatP at 2.8 Å resolution, which revealed a hexameric UreI-like channel structure. It has six TMSs surrounding the central channel pore in each protomer and three conserved hydrophobic residues, FLY, located in the middle of the TMS region for pore constriction. According to single-channel conductance recordings, performed with purified SatP reconstituted into lipid bilayers, three conserved polar residues in TMS1, facing the periplasmic side, are closely associated with acetate translocation activity (Sun et al. 2018).  Wu et al. 2019 suggested that channel opening results from the repacking of key residues, such as Gln50 and Phe17, as well as the subsequent outward movement of all transmembrane helices. Their simulations suggested that acetate is always surrounded by several water molecules when passing through the channel. A high energy barrier of 15 kcal/mol was measured.  This fact and the results observed for fungal homologues suggest that a carrier mechanism rather than a channel mechanism is operative.  

Ato1, Ato2, Ato3, and Ato6 in Candida albicans exhibit distinct cellular localization and expression levels in the plasma membrane, depending on the presence or absence of monocarboxylates. Deletion of ATO1 impaired Ato2 and Ato3 protein expression and caused ER retention of a distinct form of Ato2, suggesting a central regulatory role for Ato1 in the Ato transport system. This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification (Ghuaemi et al., 2025 - 2026, personal communication).