Functional and structural asymmetry suggest a unifying principle for catalysis in membrane-bound pyrophosphatases.

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 co

SUBMITTER: Strauss J 

PROVIDER: S-EPMC10897367 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature