8B37

Crystal structure of Pyrobaculum aerophilum potassium-independent proton pumping membrane integral pyrophosphatase in complex with imidodiphosphate and magnesium, and with bound sulphate

Summary for 8B37

• Entry DOI: 10.2210/pdb8b37/pdb
• Descriptor: K(+)-insensitive pyrophosphate-energized proton pump, MAGNESIUM ION, IMIDODIPHOSPHORIC ACID, ... (5 entities in total)
• Functional Keywords: k+-independence, ion-selectivity, membrane proteins, membrane-bound pyrophosphatases., membrane protein
• Biological source: Pyrobaculum aerophilum
• Total number of polymer chains: 2
• Total formula weight: 153466.38

Authors

Strauss, J.,Wilkinson, C.,Vidilaseris, K.,Ribeiro, O.,Liu, J.,Hillier, J.,Malinen, A.,Gehl, B.,Jeuken, L.C.,Pearson, A.R.,Goldman, A. (deposition date: 2022-09-16, release date: 2024-01-17, Last modification date: 2024-02-21)

Primary citation

Strauss, J.,Wilkinson, C.,Vidilaseris, K.,de Castro Ribeiro, O.M.,Liu, J.,Hillier, J.,Wichert, M.,Malinen, A.M.,Gehl, B.,Jeuken, L.J.,Pearson, A.R.,Goldman, A.
Functional and structural asymmetry suggest a unifying principle for catalysis in membrane-bound pyrophosphatases.
Embo Rep., 25:853-875, 2024

PubMed Abstract: 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.

PubMed: 38182815
DOI: 10.1038/s44319-023-00037-x

Experimental method

X-RAY DIFFRACTION (3.84 Å)