title: Structure and regulation of the V-ATPases.
abstract: The V-ATPases are ATP-dependent proton pumps present in both intracellular compartments and the plasma membrane. They function in such processes as membrane traffic, protein degradation, renal acidification, bone resorption and tumor metastasis. The V-ATPases are composed of a peripheral V(1) domain responsible for ATP hydrolysis and an integral V(0) domain that carries out proton transport. Our recent work has focused on structural analysis of the V-ATPase complex using both cysteine-mediated cross-linking and electron microscopy. For cross-linking studies, unique cysteine residues were introduced into structurally defined sites within the B and C subunits and used as points of attachment for the photoactivated cross-linking reagent MBP. Disulfide mediated cross-linking has also been used to define helical contact surfaces between subunits within the integral V(0) domain. With respect to regulation of V-ATPase activity, we have investigated the role that intracellular environment, luminal pH and a unique domain of the catalytic A subunit play in controlling reversible dissociation in vivo.
authors.affiliation: Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, Massachusetts 02111, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: Jefferies
authors.forename: Jie
authors.initials: J
authors.lastname: Qi
authors.forename: Ayana
authors.initials: A
authors.lastname: Hinton
authors.forename: Michael
authors.initials: M
authors.lastname: Forgac
mesh_terms: D000818:Animals; D006801:Humans; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D025262:Vacuolar Proton-Translocating ATPases