Probing the Interactions of Carboxy-atractyloside and Atractyloside with the Yeast Mitochondrial ADP/ATP Carrier

被引：35

作者：

Kedrov, Alexej ^{[2
]}

Hellawell, Alex M. ^{[1
]}

Klosin, Adam ^{[2
]}

Broadhurst, R. Bill ^{[3
]}

Kunji, Edmund R. S. ^{[1
]}

Mueller, Daniel J. ^{[2
,4
]}

机构：

[1] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England

[2] Tech Univ Dresden, Ctr Biotechnol, Cellular Machines Grp, D-01307 Dresden, Germany

[3] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

[4] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland

来源：

STRUCTURE | 2010年 / 18卷 / 01期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

ATOMIC-FORCE MICROSCOPY; MOLECULAR-INTERACTIONS; ADENINE-NUCLEOTIDES; LIVER MITOCHONDRIA; MEMBRANE-PROTEINS; ENERGY LANDSCAPE; BINDING; ANTIPORTER; SUBSTRATE; ADP;

D O I：

10.1016/j.str.2009.11.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mitochondrial ADP/ATP carriers are inhibited by two natural compounds, atractyloside (ATR) or carboxyatractyloside (CATR), which differ by one carboxylate group. The interactions of the inhibitors with the carrier were investigated by single-molecule force spectroscopy. Transmembrane alpha helices of the ATR-inhibited carrier displayed heterogeneous mechanical and kinetic properties. Whereas alpha helix H2 showed the most brittle mechanical properties and lowest kinetic stability, alpha helix H5 was mechanically the most flexible and possessed a kinetic stability 9 orders of magnitude greater than that of alpha helix H2. In contrast, CATR-binding substantially increased the kinetic stability of alpha helix H2 and tuned the mechanical flexibility of alpha helices H5 and H6. NMR spectroscopy confirmed that the additional carboxylate group of CATR binds to the sixth alpha helix, indicating that the enhanced stability of H2 is mediated via interactions between CATR and H6.

引用

页码：39 / 46

页数：8

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