Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's A{beta} peptide

Journal Article · Fri Jun 10 00:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.04.141· OSTI ID:22204950

Garvey, Megan; Tepper, Katharina ^[1]; Haupt, Caroline ^[2]; Knuepfer, Uwe ^[3]; Klement, Karolin; Meinhardt, Jessica ^[4]; Horn, Uwe ^[3]; Balbach, Jochen ^[2]; Faendrich, Marcus ^[1]

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1. Max-Planck-Forschungsstelle fuer Enzymologie der Proteinfaltung, Weinbergweg 22, D-06120 Halle (Saale) (Germany)
2. Institute fuer Physik, Biophysik, Martin-Luther Universitaet Halle-Wittenberg, Betty-Heimann-Str. 7, D-06120 Halle (Saale) (Germany)
3. Leibniz-Institute for Infection Biology and Natural Product Research, Beutenbergstr. 11a, D-07745 Jena (Germany)
4. Leibniz-Institute for Age Research (FLI), Beutenbergstr. 11, D-07745 Jena (Germany)

Highlights: {yields} Sodium phosphate buffer accelerated A{beta}(1-40) nucleation relative to HEPES. {yields} A{beta}(1-40) fibrils formed in the two buffers show only minor structural differences. {yields} NMR revealed that A{beta}(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of A{beta} peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of A{beta} and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of A{beta} peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of A{beta} fibrillation. The three histidine residues at positions 6, 13 and 14 of A{beta}(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

• OSTI ID: 22204950
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 409, Issue 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BUFFERS
DMSO
FIBERS
FLUORESCENCE
FOURIER TRANSFORMATION
HISTIDINE
IN VITRO
INFRARED SPECTRA
NERVOUS SYSTEM DISEASES
NUCLEAR MAGNETIC RESONANCE
NUCLEATION
PEPTIDES
PH VALUE
SODIUM PHOSPHATES
SPECTROSCOPY
SULFONIC ACIDS
TRANSMISSION ELECTRON MICROSCOPY
X RADIATION
X-RAY DIFFRACTION