title: Valine 181 is critical for the nucleotide exchange activity of human mitochondrial ADP/ATP carriers in yeast.
abstract: We isolated yeast Saccharomyces cerevisiae cells transformed with one of the three human adenine nucleotide carrier genes (HANC) that exhibited higher growth capacity than previously observed. The HANC genes were isolated from these clones, and we identified two independent mutations of HANC that led to replacement of valine 181 located in the fourth transmembrane segment by methionine or phenylalanine. Tolerance of this position toward substitution with various amino acids was systematically investigated, and since HANC/V181M was among the most efficient in growth complementation, it was more extensively studied. Here we show that increased growth capacities were associated with higher ADP/ATP exchange activities and not with higher human carrier amount in yeast mitochondria. These results are discussed in the light of the bovine Ancp structure, that shares more than 90% amino acid identity with Hancps, and its interaction with the lipid environment.
authors.affiliation: Laboratoire de Physiologie Moléculaire et Cellulaire, IBGC-CNRS, UMR 5095, 1 rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Carine
authors.initials: C
authors.lastname: De Marcos Lousa
authors.forename: Véronique
authors.initials: V
authors.lastname: Trézéguet
authors.forename: Claudine
authors.initials: C
authors.lastname: David
authors.forename: Vincent
authors.initials: V
authors.lastname: Postis
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnou
authors.forename: Eva
authors.initials: E
authors.lastname: Pebay-Peyroula
authors.forename: Gérard
authors.initials: G
authors.lastname: Brandolin
authors.forename: Guy J-M
authors.initials: GJ
authors.lastname: Lauquin
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism*; D033742:Adenine Nucleotide Translocator 2 / Q000235:genetics / Q000378:metabolism*; D033781:Adenine Nucleotide Translocator 3 / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002417:Cattle; D005816:Genetic Complementation Test; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays; D014633:Valine / Q000235:genetics
chemical_list: D033741:Adenine Nucleotide Translocator 1; D033742:Adenine Nucleotide Translocator 2; D033781:Adenine Nucleotide Translocator 3; D020662:Guanine Nucleotide Exchange Factors; D029701:Saccharomyces cerevisiae Proteins; D000226:Mitochondrial ADP, ATP Translocases; D008715:Methionine; D014633:Valine