Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity

Journal of Molecular Biology
Agata RekasJ A Carver

Abstract

alpha-Synuclein is a pre-synaptic protein, the function of which is not completely understood, but its pathological form is involved in neurodegenerative diseases. In vitro, alpha-synuclein spontaneously forms amyloid fibrils. Here, we report that alphaB-crystallin, a molecular chaperone found in Lewy bodies that are characteristic of Parkinson's disease (PD), is a potent in vitro inhibitor of alpha-synuclein fibrillization, both of wild-type and the two mutant forms (A30P and A53T) that cause familial, early onset PD. In doing so, large irregular aggregates of alpha-synuclein and alphaB-crystallin are formed implying that alphaB-crystallin redirects alpha-synuclein from a fibril-formation pathway towards an amorphous aggregation pathway, thus reducing the amount of physiologically stable amyloid deposits in favor of easily degradable amorphous aggregates. alpha-Synuclein acts as a molecular chaperone to prevent the stress-induced, amorphous aggregation of target proteins. Compared to wild-type alpha-synuclein, both mutant forms have decreased chaperone activity in vitro against the aggregation of reduced insulin at 37 degrees C and the thermally induced aggregation of betaL-crystallin at 60 degrees C. Wild-type alpha-synuclein...Continue Reading

References

Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K UédaT Saitoh
Nov 22, 1997·FEBS Letters·Y C KudvaN L Eberhardt
Nov 13, 1998·Current Opinion in Neurobiology·M GoedertS W Davies
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·L C SerpellR A Crowther
Jun 1, 2000·FEBS Letters·J M SouzaH Ischiropoulos
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·P J MuchowskiF U Hartl
Jan 22, 2001·The Journal of Biological Chemistry·V N UverskyA L Fink
May 23, 2002·Biochemistry·A Keith DunkerZoran Obradović

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Citations

Dec 6, 2011·Cancer Metastasis Reviews·H AntonyA L Munn
Mar 7, 2009·Journal of Molecular Neuroscience : MN·Michael RiedelChristiane Richter-Landsberg
Mar 27, 2012·Journal of Agricultural and Food Chemistry·Tomas KoudelkaJohn A Carver
Oct 7, 2005·The New England Journal of Medicine·Alberto J L Macario, Everly Conway de Macario
May 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Amy L RobertsonStephen P Bottomley
Dec 4, 2009·The Journal of Biological Chemistry·Katja SkergetEva Zerovnik
May 14, 2008·Molecular & Cellular Proteomics : MCP·Francesca LavatelliCatherine E Costello
Jan 18, 2005·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Alberto J L MacarioEverly Conway de Macario
Mar 27, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Serena CarraAngelo Poletti
Nov 28, 2007·Annual Review of Pathology·Daniel M SkovronskyJohn Q Trojanowski
Jul 26, 2012·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Hemi DimantPamela J McLean
Mar 29, 2008·PLoS Computational Biology·Hedi Hegyi, Peter Tompa
Oct 13, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yousuf O AliR Grace Zhai
Jan 4, 2007·International Journal of Biological Sciences·Guang-Rui LuoWei-Dong Le
Nov 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jennifer C LeeJay R Winkler
Apr 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Georg K A HochbergArthur Laganowsky
Mar 25, 2010·Pharmaceutical Research·Tue RasmussenWim Jiskoot
Mar 1, 2014·Progress in Biophysics and Molecular Biology·Wilbert C Boelens
Oct 30, 2014·Cellular and Molecular Life Sciences : CMLS·Teresa M TreweekJohn A Carver
Jan 17, 2012·Journal of Molecular Biology·Torleif Härd, Christofer Lendel
Oct 13, 2015·Nature Structural & Molecular Biology·Andi MainzBernd Reif
Nov 15, 2008·Experimental Eye Research·Jochen Graw
Sep 1, 2015·Biochimica Et Biophysica Acta·Nicholas J RayJohn A Carver
Jul 12, 2007·Journal of Neurochemistry·Vladimir N Uversky
Mar 29, 2007·Brain Pathology·James B LeverenzJing Zhang
Jun 29, 2014·Biochimica Et Biophysica Acta·Dezerae CoxHeath Ecroyd
Apr 18, 2016·Cellular and Molecular Life Sciences : CMLS·Britta Bartelt-KirbachNikola Golenhofen
Apr 17, 2012·Journal of Biomedicine & Biotechnology·Nguyen Trong TueMasamitsu Yamaguchi
Jun 1, 2016·Frontiers in Molecular Biosciences·Robert KisilevskyVittorio Bellotti
Oct 4, 2005·FEBS Letters·Guihong SunGengfu Xiao
Aug 16, 2016·Cellular and Molecular Life Sciences : CMLS·Sandeep K Sharma, Smriti Priya

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