High-chloride concentrations abolish the binding of adenine nucleotides in the mitochondrial ADP/ATP carrier family.
The ADP/ATP carrier (AAC) is a very effective membrane protein that mediates the exchange of ADP and ATP across the mitochondrial membrane. In vivo transport measurements on the AAC overexpressed in Escherichia coli demonstrate that this process can be severely inhibited by high-chloride concentrations. Molecular-dynamics simulations reveal a strong modification of the topology of the local electric field related to the number of chloride ions inside the cavity. Halide ions are shown to shield the positive charges lining the internal cavity of the carrier by accurate targeting of key basic residues. These specific amino acids are highly conserved as highlighted by the analysis of multiple AAC sequences. These results strongly suggest that the chloride concentration acts as an electrostatic lock for the mitochondrial AAC family, thereby preventing adenine nucleotides from reaching their dedicated binding sites.
Krammer
Eva-Maria
EM
Equipe de Dynamique des Assemblages Membranaires, UMR No. 7565, Centre National de la Recherche Scientifique-Université Henri Poincaré, Nancy, France.
Ravaud
Stéphanie
S
Dehez
François
F
Frelet-Barrand
Annie
A
Pebay-Peyroula
Eva
E
Chipot
Christophe
C
D000227:Adenine Nucleotides / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis; D029681:Arabidopsis Proteins / Q000737:chemistry; D002417:Cattle; D002712:Chlorides / Q000737:chemistry*; D003198:Computer Simulation; D017124:Conserved Sequence; D004574:Electromagnetic Fields; D004926:Escherichia coli; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012965:Sodium Chloride / Q000737:chemistry; D055672:Static Electricity; D013997:Time Factors
D000227:Adenine Nucleotides; D029681:Arabidopsis Proteins; D002712:Chlorides; D011994:Recombinant Proteins; D012965:Sodium Chloride; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases