Valine 181 is critical for the nucleotide exchange activity of human mitochondrial ADP/ATP carriers in yeast.

Carine de Marcos Lousa (1) , Véronique Trézéguet (1) , Claudine David (1) , Vincent Postis (1) , Bertrand Arnou (2, 3, 4) , Eva Pebay-Peyroula (5) , Gérard Brandolin (6) , Guy J-M Lauquin (1)

1 IBGC - Institut de biochimie et génétique cellulaires
2 inconnu
3 SMPSD - Système membranaires, photobiologie, stress et détoxication
4 IBITECS - Institut de Biologie et de Technologies de Saclay
5 LPM - Laboratoire des Protéines Membranaires
6 BBSI - Biochimie et biophysique des systèmes intégrés

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.

Domaines: Biochimie [q-bio.BM]

Carine de Marcos Lousa, Véronique Trézéguet, Claudine David, Vincent Postis, Bertrand Arnou, et al.. Valine 181 is critical for the nucleotide exchange activity of human mitochondrial ADP/ATP carriers in yeast.. Biochemistry, 2005, 44 (11), pp.4342-8. ⟨10.1021/bi0475370⟩. ⟨hal-00376047⟩