title: Protein-protein interactions within the ensemble, eukaryotic V-ATPase, and its concerted interactions with cellular machineries.
abstract: The V1VO-ATPase (V-ATPase) is the important proton-pump in eukaryotic cells, responsible for pH-homeostasis, pH-sensing and amino acid sensing, and therefore essential for cell growths and metabolism. ATP-cleavage in the catalytic A3B3-hexamer of V1 has to be communicated via several so-called central and peripheral stalk units to the proton-pumping VO-part, which is membrane-embedded. A unique feature of V1VO-ATPase regulation is its reversible disassembly of the V1 and VO domain. Actin provides a network to hold the V1 in proximity to the VO, enabling effective V1VO-assembly to occur. Besides binding to actin, the 14-subunit V-ATPase interacts with multi-subunit machineries to form cellular sensors, which regulate the pH in cellular compartments or amino acid signaling in lysosomes. Here we describe a variety of subunit-subunit interactions within the V-ATPase enzyme during catalysis and its protein-protein assembling with key cellular machineries, essential for cellular function.
authors.affiliation: Nanyang Technological University, Division of Structural Biology and Biochemistry, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.
authors.forename: Asha Manikkoth
authors.initials: AM
authors.lastname: Balakrishna
authors.affiliation: Nanyang Technological University, Division of Structural Biology and Biochemistry, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.
authors.forename: Malathy Sony Subramanian
authors.initials: MS
authors.lastname: Manimekalai
authors.affiliation: Nanyang Technological University, Division of Structural Biology and Biochemistry, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Republic of Singapore. Electronic address: ggrueber@ntu.edu.sg.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Grüber
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D056890:Eukaryota / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011522:Protons
chemical_list: D021122:Protein Subunits; D011522:Protons; D000251:Adenosine Triphosphatases
keywords: Bioenergetics; Coupling; Molecular engine; Saccharomyces cerevisiae; Structural biology; V-ATPase; Vacuolar ATPase