Stopped-flow kinetics reveal multiple phases of thioflavin T binding to Alzheimer beta (1-40) amyloid fibrils

Archives of Biochemistry and Biophysics
H LeVine

Abstract

The benzothiazole dye thioflavin T (ThT) is a classical amyloid stain for senile plaques containing beta/A4 peptide in Alzheimer's disease brain. ThT also binds rapidly and specifically to the anti-parallel beta-sheet fibrils formed from synthetic beta (1-40) peptide, but does not bind to monomer or oligomeric intermediates. The fibrillar beta-sheet-bound dye species undergoes a characteristic 120 nm red shift of its excitation spectrum that may be selectively excited at 450 nm, resulting in a fluorescence signal at 482 nm. Mixing of preformed beta (1-40) amyloid fibrils with ThT in a stopped-flow spectrophotometer, monitoring fluorescence emission at > 475 nm while exciting at 450 nm, distinguished multiple kinetic phases of roughly equivalent amplitude with tau's in the ranges of 0.007, 0.05, 0.75, and 10-20 s. The fastest reaction appears to reflect a bimolecular dye binding event while the remaining reactions are rate-limited by protein tertiary or quaternary conformational changes. The high activation energies of the three slower reactions support this interpretation. The ThT concentration dependence of the reaction rates at different ratios of ThT/beta (1-40) amyloid fibrils rules out a rate-limiting conformational change...Continue Reading

References

Apr 1, 1991·Neuron·D J Selkoe
Aug 1, 1989·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·W E KlunkD J Abraham
Aug 1, 1989·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·W E KlunkD J Abraham
Nov 1, 1989·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·P L McGeerE G McGeer
Apr 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·A RoherD KuKuruga
Dec 15, 1974·Journal of Molecular Biology·R HartmanJ Hermans
Oct 1, 1972·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·G G GlennerD L Page
Jan 18, 1972·Biochemistry·G M Loudon, D E Koshland
Oct 1, 1994·Current Opinion in Neurobiology·R Katzman
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·A LomakinD B Teplow
Aug 2, 1996·The Journal of Biological Chemistry·D J Selkoe
Mar 1, 1997·Nature Biotechnology·W P EslerJ E Maggio

❮ Previous
Next ❯

Citations

Feb 11, 2009·Journal of Biochemistry·Koichi MorimotoBen'ichiro Tonomura
Feb 4, 2016·Biophysical Journal·Kadi-Liis SaarTuomas P J Knowles
Aug 8, 2007·Journal of Structural Biology·Minna GroenningSven Frokjaer
Mar 15, 2008·Biophysical Journal·M Soledad CelejThomas M Jovin
Mar 17, 2007·Scandinavian Journal of Clinical and Laboratory Investigation·M L SelenicaA Grubb
May 7, 1999·Japanese Journal of Pharmacology·T KiharaA Akaike
Nov 18, 2010·Biophysical Journal·Alexander K BuellMark E Welland
May 17, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Zhe QinGang Ma
Dec 3, 2005·Journal of Molecular Biology·Jesper Søndergaard PedersenDaniel Erik Otzen
Jan 31, 2015·Metallomics : Integrated Biometal Science·Marek LuczkowskiDaniela Valensin
Mar 19, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Anyang SunGuoying Bing
Oct 7, 2016·Chemical Communications : Chem Comm·Aruna K MoraSukhendu Nath
Mar 16, 2018·Chemistry : a European Journal·Jun ZhangPer Hammarström
Feb 9, 2018·Protein Science : a Publication of the Protein Society·Wai-Ming Yau, Robert Tycko
May 27, 2016·PloS One·Anna I SulatskayaKonstantin K Turoverov
Feb 20, 2008·Chembiochem : a European Journal of Chemical Biology·Anasztázia HetényiBotond Penke
Nov 3, 2010·Chirality·Antonio Mario TamburroBrigida Bochicchio
Jun 25, 2009·Journal of Biosciences·Lia MillucciAnnalisa Santucci
Jun 22, 2006·The Journal of Biological Chemistry·Ping YanJin-Moo Lee
Aug 10, 2007·The Journal of Biological Chemistry·Isobel J MortenEric W Hewitt
Aug 4, 2005·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Harry LeVine
Mar 10, 2001·Reviews in the Neurosciences·P K Panegyres
May 18, 2012·Molecular Neurobiology·Irina M KuznetsovaKonstantin K Turoverov
Jun 9, 2020·Chemical Communications : Chem Comm·Benedikt FriegHolger Gohlke
Oct 26, 2001·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Y M LinF J Stevens
Jul 24, 2013·Chemical Communications : Chem Comm·Nolene ByrneMaria Forsyth
Mar 28, 2001·Annals of the New York Academy of Sciences·B D GitterC D Carlson
Dec 14, 2018·Chemical Science·Alejandro LamasJuan R Granja
Dec 2, 2020·International Journal of Molecular Sciences·Kamile MikalauskaiteVytautas Smirnovas
Dec 6, 2020·International Journal of Biological Macromolecules·Ritutama GhoshNand Kishore
Feb 10, 2011·Archives of Biochemistry and Biophysics·Valeria VetriValeria Militello
Oct 30, 2008·The Journal of Physical Chemistry. B·Vito FoderàMaurizio Leone
Apr 16, 2009·The Journal of Physical Chemistry. B·Vitali I StsiapuraKonstantin K Turoverov
Aug 28, 1999·Bioorganic & Medicinal Chemistry Letters·W Garzon-RodriguezC G Glabe
Jul 10, 1999·Neuroscience Letters·S C Bondy, A Truong
Jul 30, 2010·The Journal of Physical Chemistry. a·Vitali I StsiapuraOleg V Buganov

❮ Previous
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