A1 Refereed original research article in a scientific journal
Functional and structural asymmetry suggest a unifying principle for catalysis in membrane-bound pyrophosphatases
Authors: Strauss Jannik, Wilkinson Craig, Vidilaseris Keni, de Castro Ribeiro Orquidea M, Liu Jianing, Hillier James, Wichert Maximilian, Malinen Anssi M, Gehl Bernadette, Jeuken Lars JC, Pearson Arwen R, Goldman Adrian
Publisher: John Wiley & Sons
Publication year: 2024
Journal: EMBO Reports
Journal name in source: EMBO reports
Volume: 25
Issue: 2
First page : 853
Last page: 875
eISSN: 1469-3178
DOI: https://doi.org/10.1038/s44319-023-00037-x
Web address : https://www.embopress.org/doi/full/10.1038/s44319-023-00037-x
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/387307272
Membrane-bound pyrophosphatases (M-PPases) are homodimeric primary ion pumps that couple the transport of Na+- and/or H+ across membranes to the hydrolysis of pyrophosphate. Their role in the virulence of protist pathogens like Plasmodium falciparum makes them an intriguing target for structural and functional studies. Here, we show the first structure of a K+-independent M-PPase, asymmetric and time-dependent substrate binding in time-resolved structures of a K+-dependent M-PPase and demonstrate pumping-before-hydrolysis by electrometric studies. We suggest how key residues in helix 12, 13, and the exit channel loops affect ion selectivity and K+-activation due to a complex interplay of residues that are involved in subunit-subunit communication. Our findings not only explain ion selectivity in M-PPases but also why they display half-of-the-sites reactivity. Based on this, we propose, for the first time, a unified model for ion-pumping, hydrolysis, and energy coupling in all M-PPases, including those that pump both Na+ and H+.
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