Restriction of access to the central cavity is a major contributor to substrate selectivity in plant ABCG transporters

Pakuła, Konrad; Sequeiros-Borja, Carlos; Biała-Leonhard, Wanda; Pawela, Aleksandra; Banasiak, Joanna; Bailly, Aurélien; Radom, Marcin; Geisler, Markus; Brezovsky, Jan; Jasiński, Michał

doi:10.1007/s00018-023-04751-6

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Pakuła, K., Sequeiros-Borja, C., Biała-Leonhard, W., Pawela, A., Banasiak, J., Bailly, A., Radom, M., Geisler, M., Brezovsky, J., & Jasiński, M. (2023). Restriction of access to the central cavity is a major contributor to substrate selectivity in plant ABCG transporters. Cellular and Molecular Life Sciences, 80(4), 105. https://doi.org/10.1007/s00018-023-04751-6

Abstract

ABCG46 of the legume Medicago truncatula is an ABC-type transporter responsible for highly selective translocation of the phenylpropanoids, 4-coumarate, and liquiritigenin, over the plasma membrane. To investigate molecular determinants of the observed substrate selectivity, we applied a combination of phylogenetic and biochemical analyses, AlphaFold2 structure prediction, molecular dynamics simulations, and mutagenesis. We discovered an unusually narrow transient access path to the central cavity of MtABCG46 that constitutes an initi