High-Chloride Concentrations Abolish the Binding of Adenine Nucleotides in the Mitochondrial ADP/ATP Carrier Family

被引：20

作者：

Krammer, Eva-Maria ^{[1
]}

Ravaud, Stephanie ^{[2
]}

Dehez, Francois ^{[1
]}

Frelet-Barrand, Annie ^{[3
]}

Pebay-Peyroula, Eva ^{[2
]}

Chipot, Christophe ^{[1
]}

机构：

[1] Univ Henri Poincare, Equipe Dynam Assemblages Membranaires, UMR 7565, CNRS, Nancy, France

[2] Univ Grenoble 1, Inst Biol Struct, UMR 5075, CEA,CNRS, Grenoble, France

[3] Univ Grenoble 1, Lab Physiol Cellulaire Vegetale, UMR 5168,Direct Sci Vivant,Inst Rech Technol & Sc, CNRS,CEA,Inst Natl Rech Agron,UMR 1200, Grenoble, France

来源：

BIOPHYSICAL JOURNAL | 2009年 / 97卷 / 10期

关键词：

MOLECULAR-DYNAMICS; RECONSTITUTED ADP; PHOSPHOLIPIDS; TRANSPORT;

D O I：

10.1016/j.bpj.2009.08.047

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

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.

引用

页码：L25 / L27

页数：3

共 16 条

[1] Imaging α-hemolysin with molecular dynamics:: Ionic conductance, osmotic permeability, and the electrostatic potential map [J].