Download MendeleyMembrane pyrophosphatases from Thermotoga maritima and Vigna radiata suggest a conserved coupling mechanism
Li, K.M., Wilkinson, C., Kellosalo, J., Tsai, J.Y., Kajander, T., Jeuken, L.J., Sun, Y.J., Goldman, A.(2016) Nat Commun 7: 13596-13596
- PubMed: 27922000
- DOI: https://doi.org/10.1038/ncomms13596
- Primary Citation of Related Structures:
5GPJ, 5LZQ, 5LZR - PubMed Abstract:
Membrane-bound pyrophosphatases (M-PPases), which couple proton/sodium ion transport to pyrophosphate synthesis/hydrolysis, are important in abiotic stress resistance and in the infectivity of protozoan parasites. Here, three M-PPase structures in different catalytic states show that closure of the substrate-binding pocket by helices 5-6 affects helix 13 in the dimer interface and causes helix 12 to move down. This springs a 'molecular mousetrap', repositioning a conserved aspartate and activating the nucleophilic water. Corkscrew motion at helices 6 and 16 rearranges the key ionic gate residues and leads to ion pumping. The pumped ion is above the ion gate in one of the ion-bound structures, but below it in the other. Electrometric measurements show a single-turnover event with a non-hydrolysable inhibitor, supporting our model that ion pumping precedes hydrolysis. We propose a complete catalytic cycle for both proton and sodium-pumping M-PPases, and one that also explains the basis for ion specificity.
Organizational Affiliation:
Department of Life Science and Institute of Bioinformatics and Structural Biology, College of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
