Mapping the nucleotide binding site of uncoupling protein 1 using atomic force microscopy.

作者: Rong Zhu , Anne Rupprecht , Andreas Ebner , Thomas Haselgrübler , Hermann J. Gruber

DOI: 10.1021/JA312550K

关键词:

摘要: A tight regulation of proton transport in the inner mitochondrial membrane is crucial for physiological processes such as ATP synthesis, heat production, or reactive oxygen species proposed uncoupling protein family members (UCP). Specific thus becoming increasingly important therapy obesity and inflammatory, neurodegenerative, ischemic diseases. We other research groups have shown previously that UCP1- UCP2-mediated inhibited by purine nucleotides. Several hypotheses been to explain inhibitory effect ATP, although structural details are still lacking. Moreover, unresolved mystery how UCP operates vivo despite permanent presence high (millimolar) concentrations mitochondria. Here we use topographic recognition (TREC) mode an atomic force microscope visualize UCP1 reconstituted into lipid bilayers analyze ATP–protein interaction at...

参考文章(36)
David G. Nicholls, Vibeke S. M. Bernson, Gillian M. Heaton, The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. Experientia. Supplementum. ,vol. 32, pp. 89- 93 ,(1978) , 10.1007/978-3-0348-5559-4_9
E. Rial, D.G. Nicholls, The regulation of the proton conductance of brown fat mitochondria FEBS Letters. ,vol. 161, pp. 284- 288 ,(1983) , 10.1016/0014-5793(83)81026-6
Anne Rupprecht, Elena A. Sokolenko, Valeri Beck, Olaf Ninnemann, Martin Jaburek, Thorsten Trimbuch, Sergey S. Klishin, Petr Jezek, Vladimir P. Skulachev, Elena E. Pohl, Role of the transmembrane potential in the membrane proton leak. Biophysical Journal. ,vol. 98, pp. 1503- 1511 ,(2010) , 10.1016/J.BPJ.2009.12.4301
M KLINGENBERG, Transport viewed as a catalytic process. Biochimie. ,vol. 89, pp. 1042- 1048 ,(2007) , 10.1016/J.BIOCHI.2007.02.010
Stefan Krauss, Chen-Yu Zhang, Bradford B. Lowell, The mitochondrial uncoupling-protein homologues. Nature Reviews Molecular Cell Biology. ,vol. 6, pp. 248- 261 ,(2005) , 10.1038/NRM1592
J. A. Harper, K. Dickinson, M. D. Brand, Mitochondrial uncoupling as a target for drug development for the treatment of obesity. Obesity Reviews. ,vol. 2, pp. 255- 265 ,(2001) , 10.1046/J.1467-789X.2001.00043.X
Martin Klingenberg, Wanderings in bioenergetics and biomembranes. Biochimica et Biophysica Acta. ,vol. 1797, pp. 579- 594 ,(2010) , 10.1016/J.BBABIO.2010.02.012
François Dehez, Eva Pebay-Peyroula, Christophe Chipot, Binding of ADP in the mitochondrial ADP/ATP carrier is driven by an electrostatic funnel Journal of the American Chemical Society. ,vol. 130, pp. 12725- 12733 ,(2008) , 10.1021/JA8033087
Andreas Ebner, Linda Wildling, A. S. M. Kamruzzahan, Christian Rankl, Jürgen Wruss, Christoph D. Hahn, Martin Hölzl, Rong Zhu, Ferry Kienberger, Dieter Blaas, Peter Hinterdorfer, Hermann J. Gruber, A New, Simple Method for Linking of Antibodies to Atomic Force Microscopy Tips Bioconjugate Chemistry. ,vol. 18, pp. 1176- 1184 ,(2007) , 10.1021/BC070030S