Kontakt zwischen den β1‐ und β2‐Segmenten von α‐Synuclein inhibiert die Amyloidbildung
作者： Hamed Shaykhalishahi , Aziz Gauhar , Michael M. Wördehoff , Clara S. R. Grüning , Antonia N. Klein
关键词:
摘要: Die Umwandlung des intrinsisch ungeordneten Proteins α-Synuclein (α-syn) in Amyloidaggregate ist ein Schlusselprozess der Parkinson-Krankheit. Sequenzregion 35–59 enthalt die β-Strangsegmente β1 und β2 aus Strukturmodellen von α-syn-Amyloidfibrillen sowie Mehrzahl bekannten krankheitsassoziierten Mutationen. gehen miteinander transiente Interaktionen monomerem α-syn ein. Hier untersuchen wir Folgen β1-β2-Kontakten mittels Disulfid-Engineering, biophysikalischen Techniken Zellviabilitats-Assays. Doppelcystein-Mutante α-synCC mit einer Disulfidbrucke zwischen bildet keine Aggregate inhibiert Aggregation Toxizitat Wildtyp-α-syn. Wir zeigen, dass Amyloid-β-Peptids Inselamyloid-Polypeptids inhibiert, Effekt, α-synCC-Mutante verstarkt ist. Tertiare β1-β2-Region beeintrachtigen Nukleation Amyloidbildung. Ein therapeutischer Ansatz ware folglich Forderung solcher Interaktionen.
sci-hub.se 参考文章(34)
J. C. Lee, R. Langen, P. A. Hummel, H. B. Gray, J. R. Winkler, α-Synuclein structures from fluorescence energy-transfer kinetics: Implications for the role of the protein in Parkinson's disease Proceedings of the National Academy of Sciences of the United States of America. ,vol. 101, pp. 16466- 16471 ,(2004) , 10.1073/PNAS.0407307101
Min Chen, Martin Margittai, Jeannie Chen, Ralf Langen, Investigation of α-Synuclein Fibril Structure by Site-directed Spin Labeling Journal of Biological Chemistry. ,vol. 282, pp. 24970- 24979 ,(2007) , 10.1074/JBC.M700368200
Yehouda Harpaz, Mark Gerstein, Cyrus Chothia, Volume changes on protein folding. Structure. ,vol. 2, pp. 641- 649 ,(1994) , 10.1016/S0969-2126(00)00065-4
Bryan Schmidt, Lorraine Ho, Philip J. Hogg, Allosteric Disulfide Bonds Biochemistry. ,vol. 45, pp. 7429- 7433 ,(2006) , 10.1021/BI0603064
Bruno Fauvet, Martial K. Mbefo, Mohamed-Bilal Fares, Carole Desobry, Sarah Michael, Mustafa T. Ardah, Elpida Tsika, Philippe Coune, Michel Prudent, Niels Lion, David Eliezer, Darren J. Moore, Bernard Schneider, Patrick Aebischer, Omar M. El-Agnaf, Eliezer Masliah, Hilal A. Lashuel, α-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. Journal of Biological Chemistry. ,vol. 287, pp. 15345- 15364 ,(2012) , 10.1074/JBC.M111.318949
Ewa A. Mirecka, Hamed Shaykhalishahi, Aziz Gauhar, Şerife Akgül, Justin Lecher, Dieter Willbold, Matthias Stoldt, Wolfgang Hoyer, Sequestration of a β-Hairpin for Control of α-Synuclein Aggregation† Angewandte Chemie. ,vol. 53, pp. 4227- 4230 ,(2014) , 10.1002/ANIE.201309001
Matthew M. Dedmon, Kresten Lindorff-Larsen, John Christodoulou, Michele Vendruscolo, Christopher M. Dobson, Mapping Long-Range Interactions in α-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations Journal of the American Chemical Society. ,vol. 127, pp. 476- 477 ,(2005) , 10.1021/JA044834J
Torleif Härd, Christofer Lendel, Inhibition of Amyloid Formation Journal of Molecular Biology. ,vol. 421, pp. 441- 465 ,(2012) , 10.1016/J.JMB.2011.12.062
Bertil Macao, Wolfgang Hoyer, Anders Sandberg, Ann-Christin Brorsson, Christopher M Dobson, Torleif Härd, Recombinant amyloid beta-peptide production by coexpression with an affibody ligand. BMC Biotechnology. ,vol. 8, pp. 82- 82 ,(2008) , 10.1186/1472-6750-8-82
Jacqueline Burré, Sandro Vivona, Jiajie Diao, Manu Sharma, Axel T. Brunger, Thomas C. Südhof, Properties of native brain α-synuclein Nature. ,vol. 498, ,(2013) , 10.1038/NATURE12125