title: Mutant residues suppressing rho(0)-lethality in Kluyveromyces lactis occur at contact sites between subunits of F(1)-ATPase.
abstract: Characterisation of 35 Kluyveromyces lactis strains lacking mitochondrial DNA has shown that mutations suppressing rho(0)-lethality are limited to the ATP1, 2 and 3 genes coding for the alpha-, beta- and gamma- subunits of mitochondrial F(1)-ATPase. All atp mutations reduce growth on glucose and three alleles, atp1-2, 1-3 and atp3-1, produce a respiratory deficient phenotype that indicates a drop in efficiency of the F(1)F(0)-ATP synthase complex. ATPase activity is needed for suppression as a double mutant containing an atp allele, together with a mutation abolishing catalytic activity, does not suppress rho(0)-lethality. Positioning of the seven amino acids subject to mutation on the bovine F(1)-ATPase structure shows that two residues are found in a membrane proximal region while five amino acids occur at a region suggested to be a molecular bearing. The intriguing juxtaposition of mutable amino acids to other residues subject to change suggests that mutations affect subunit interactions and alter the properties of F(1) in a manner yet to be determined. An explanation for suppressor activity of atp mutations is discussed in the context of a possible role for F(1)-ATPase in the maintenance of mitochondrial inner membrane potential.
authors.affiliation: Molecular Genetics and Evolution Group, Research School of Biological Sciences, The Australian National University, PO Box 475, Canberra City, ACT, Australia. dcw@rsbs.anu.edu.au
authors.forename: G D
authors.initials: GD
authors.lastname: Clark-Walker
authors.forename: P M
authors.initials: PM
authors.lastname: Hansbro
authors.forename: F
authors.initials: F
authors.lastname: Gibson
authors.forename: X J
authors.initials: XJ
authors.lastname: Chen
mesh_terms: D000483:Alleles; D003461:Crystallography; D005804:Genes, Lethal; D016153:Genes, Suppressor; D005838:Genotype; D007716:Kluyveromyces / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics*
chemical_list: D006180:Proton-Translocating ATPases