Aluminum does not play any role in essential biological processes, but in acidic conditions it becomes biologically reactive and highly toxic even at low concentrations. Eukaryotes have developed numerous strategies for detoxification, one of which relies on membrane proteins. Fungi possess so-called aluminum resistance proteins (Alr1/2p), which are distant homologs of CorA Mg²⁺-channels but are claimed to confer resistance to aluminum. However, the mechanism behind this resistance remains poorly understood. In this study we aimed to conduct a thorough functional and structural characterization of Alr1p from Pichia pastoris (PpAlr1p). Our results confirm that PpAlr1p similar to other members of the CorA family functions as a pentamer and can mediate Zn²⁺ and Cd²⁺ transport across the membrane independently from a pH gradient. Studies on the truncated version of PpAlr1p define the core functional unit of CorA proteins but pinpoint that the intracellular domain is important for the correct localization. Competitive uptake assays with Al³⁺ showed aluminum to activate the transport of divalent cations in PpAlr1p. In addition, the growth assay of the ALR2 knock-out Saccharomyces cerevisiae strain indicates some role of Alr2p in promoting tolerance to Ni²⁺. Together, these results provide the functional and structural characterization of a eukaryotic CorA-like aluminum resistance protein, highlight the role of its N-terminal domain in proper cellular localization and define the functional core of the CorA family.

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Journal Article

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Stehantsev P, Stetsenko A, Herynková P, Zupnik A, Takens C, Zimmermannova O, Sychrova H, Guskov A

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