Equipe de Dynamique des Assemblages Membranaires, UMR No. 7565, Centre National de la Recherche Scientifique-Université Henri Poincaré, Nancy, France.
Biophys J. 2009 Nov 18;97(10):L25-7. doi: 10.1016/j.bpj.2009.08.047.
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.
ADP/ATP 载体 (AAC) 是一种非常有效的膜蛋白,介导 ADP 和 ATP 在线粒体膜之间的交换。在大肠杆菌中过表达的 AAC 的体内转运测量表明,该过程会被高氯浓度严重抑制。分子动力学模拟揭示了与腔内氯离子数量相关的局部电场拓扑结构的强烈变化。卤化物离子通过精确靶向载体内部腔的关键碱性残基来屏蔽排列在内腔的正电荷。这些特定的氨基酸高度保守,这一点通过对多个 AAC 序列的分析得到了强调。这些结果强烈表明,氯离子浓度作为线粒体 AAC 家族的静电锁,从而防止腺嘌呤核苷酸到达其专用结合位点。