New insights into structure‐function relationships between archeal ATP synthase (A₁A₀) and vacuolar type ATPase (V₁V₀)

Abstract

Adenosine triphosphate, ATP, is the energy currency of living cells. While ATP synthases of archae and ATP synthases of pro- and eukaryotic organisms operate as energy producers by synthesizing ATP, the eukaryotic V-ATPase hydrolyzes ATP and thus functions as energy transducer. These enzymes share features like the hydrophilic catalytic- and the membrane-embedded ion-translocating sector, allowing them to operate as nano-motors and to transform the transmembrane electrochemical ion gradient into ATP or vice versa. Since archaea are rooted close to the origin of life, the A-ATP synthase is probably more similar in its composition and function to the "original" enzyme, invented by Nature billion years ago. On the contrary, the V-ATPases have acquired specific structural, functional and regulatory features during evolution. This review will summarize the current knowledge on the structure, mechanism and regulation of A-ATP synthases and V-ATPases. The importance of V-ATPase in pathophysiology of diseases will be discussed.

Osteopetrosis Mutation R444L Causes Endoplasmic Reticulum Retention and Misprocessing of Vacuolar H+-ATPase a3 Subunit

“…2 are evolutionarily conserved proton pumps that, in eukaryotic cells, are responsible for acidification of intracellular compartments, such as the Golgi apparatus, endosomes, lysosomes, secretory vesicles, and vacuoles (1)(2)(3)(4)(5). In some specialized cells, like bone-resorbing osteoclasts, they are also targeted to the plasma membrane (6 -9).…”

“…Other a3 functions, such as its involvement in lysosomal acidification * This work was supported in part by Operating Grant FRN-79322 from the Canadian Institutes of Health Research. 1 2 The abbreviations used are: V-ATPase, vacuolar-type H ϩ -ATPase; LAMP2, lysosome-associated membrane protein 2; RANKL, receptor activator for nuclear factor B ligand; TPCK, tosyl phenylalanyl chloromethyl ketone; TM, transmembrane ␣-helix; CFTR, cystic fibrosis transmembrane conductance regulator; ARO, autosomal recessive osteopetrosis; PNGase F, peptide N-glycosidase F; Endo H, endo-␤-N-acetylglucosaminidase H; BMM, bone marrow mononuclear; ER, endoplasmic reticulum; ERAD, endoplasmic reticulum-associated degradation.…”

Structural insight into the motor protein A1A0ATP synthase and implications in coupling events

“…Among the outstanding problems identified by a critical assessment are amount and position of the water molecules. A variety of techniques were examined and both models and molecular parameters were analyzed: Conventional and ab initio modeling approaches signify satisfactory agreement between crystal-and SAXS-based protein models, provided hydration contributions and other precautions are taken into account [1]. Recourse to crystallographic data also allows hydrodynamic modeling; in the case of multibead assemblages novel modeling refinements (efficient bead reductions) have to be adopted [2, 3].…”

“…Examples presented include proteins ranging from simple proteins to complex, multisubunit, liganded proteins in the MDa range, and water-channel proteins as well. [1] The potential virulence factor, CFP-10/ESAT-6 complex of Mycobacterium tuberculosis belonging to the WXG-100 protein family has been studied extensively in the last decades. Although the solution structure of the complex has been published the function of this complex still remains unclear.…”

“…The enzyme is composed of an A 3 B 3 headpiece, a central and two peripheral stalks, an ion-translocating part A O , and a collar-like structure, formed by subunit E. The central stalk is made of subunits C-F, whereby the peripheral stalks are formed by the subunits H and a, respectively. ATP is synthesized on the A 3 :B 3 headpiece and the energy provided for that process is transfered to the membrane-bound A O domain [1]. The energy coupling between the two active domains occurs via the stalk part(s).…”