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bioRxiv · 10.1101/2024.03.16.584933

Selectivity and evolution of Aqp10 in solute permeability influenced by pore molecular weight

Nagashima, A.·Ushio, K.·Nishihara, H.·Akimoto, J.·Kato, A.·Furuta, T.
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Abstract

Aqp10 is an aquaglyceroporin that transports not only water but also uncharged low-molecular-weight compounds. We previously demonstrated the evolution of solute permeability in Aqp10 paralogs and showed that the urea and boric acid permeabilities of Aqp10.2 were much weaker than those of Aqp10.1 and plesiomorphic Aqp10s. However, the molecular mechanism responsible for the weak permeability of Aqp10.2 to urea and boric acid remains unclear. Herein, we present a novel hypothesis that explains the solute selectivity of Aqp10. We deduced the ancestral sequences of Aqp10.1 and Aqp10.2 paralogs via molecular phylogenetic analysis. Constructed structural models of these sequences revealed that both the well known amino acid site at position 3 and the sum of molecular weights of the four amino acid sites in the ar/R region were important for the formation of the Aqp10 selectivity filter. Site-directed mutagenesis revealed that a decrease in the sum of the molecular weights of the four amino acid sites enhanced the Aqp10 permeability to urea and boric acid. Based on this, we proposed a model in which the presence of two or more bulky amino acids in the ar/R region, which increases the sum of the molecular weights of amino acids in the ar/R region, was essential for the formation of a filter that limited urea and boric acid transport. Our results outline the molecular mechanism by which Aqp10.2 acquired a selectivity filter during evolution and provide structural insights into the narrowly tuned filter responsible for the solute selectivity of aquaglyceroporins. Significance StatementIn aquaglyceroporins, particularly Aqp10s, the urea and boric acid permeabilities of Aqp10.2 paralogs are much weaker than those of plesiomorphic Aqp10s. Here, we deduced the ancestral sequences of Aqp10.1 and Aqp10.2 via molecular phylogenetic analysis. Structural models of these sequences revealed that the sum of the four amino acid site molecular weights in the ar/R region, if more than one is bulky, contributed to the selectivity filter formation in the pore region. Using site-directed mutagenesis, reduction in the molecular weight of one bulky amino acid residue in the ar/R region restricted urea and boric acid permeability. Therefore, Aqp10.2 acquired a selectivity filter during evolution, and structural differences in this selectivity filter are responsible for the variable solute permeability of aquaglyceroporins.

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Nagashima, A., Ushio, K., Nishihara, H., Akimoto, J., Kato, A., Furuta, T.. 2024-03-17. Selectivity and evolution of Aqp10 in solute permeability influenced by pore molecular weight. https://doi.org/10.1101/2024.03.16.584933

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