Publication

Kinetic Modelling of Transport Inhibition by Substrates in ABC Importers

de Boer, M., Cordes, T. & Poolman, B., 18-Sep-2020, In : Journal of Molecular Biology. 432, 20, p. 5565-5576 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

Prokaryotic ATP-binding cassette (ABC) importers require a substrate-binding protein (SBP) for the capture and delivery of the cognate substrate to the transmembrane domain (TMD) of the transporter. Various biochemical compounds have been identified that bind to the SBP but are not transported. The mechanistic basis for the ‘non-cognate’ substrates not being transported differs. Some non-cognate substrates fail to trigger the appropriate conformational change in the SBP, resulting in loss of affinity for the TMD or the inability to allosterically activate transport. In another mechanism, the SBP cannot release the bound non-cognate substrate. Here, we used rate equations to derive the steady-state transport rate of cognate substrates of an ABC importer and investigated how non-cognate substrates influence this rate. We found that under limiting non-cognate substrate concentrations, the transport rate remains unaltered for each of the mechanisms. In contrast, at saturating substrate and SBP concentrations, the effect of the non-cognate substrate depends heavily on the respective mechanism. For instance, the transport rate becomes zero when the non-cognate substrate cannot be released by the SBP. Yet it remains unaffected when substrate release is possible but the SBP cannot dock onto the TMDs. Our work shows how the different mechanisms of substrate inhibition impact the transport kinetics, which is relevant for understanding and manipulating solute fluxes and hence the propagation of cells in nutritionally complex milieus.
Original languageEnglish
Pages (from-to)5565-5576
Number of pages12
JournalJournal of Molecular Biology
Volume432
Issue number20
Early online date12-Aug-2020
Publication statusPublished - 18-Sep-2020

    Keywords

  • ABC importers, kinetic modelling, membrane transport, rate equations, substrate-binding proteins

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