The Protein Journal

, Volume 26, Issue 6, pp 423–433

Correlation Between Thermal Aggregation and Stability of Lysozyme with Salts Described by Molar Surface Tension Increment: An Exceptional Propensity of Ammonium Salts as Aggregation Suppressor

  • Atsushi Hirano
  • Hiroyuki Hamada
  • Tatsunori Okubo
  • Takumi Noguchi
  • Hiroki Higashibata
  • Kentaro Shiraki
Article

DOI: 10.1007/s10930-007-9082-3

Cite this article as:
Hirano, A., Hamada, H., Okubo, T. et al. Protein J (2007) 26: 423. doi:10.1007/s10930-007-9082-3

Abstract

Protein aggregation is a critical problem for biotechnology and pharmaceutical industries. Despite the fact that soluble proteins have been used for many applications, our understanding of the effect of the solution chemistry on protein aggregation still remains to be elucidated. This paper investigates the process of thermal aggregation of lysozyme in the presence of various types of salts. The simple law was found; the aggregation rate of lysozyme increased with increasing melting temperature of the protein (Tm) governed by chemical characteristics of additional salts. Ammonium salts were, however, ruled out; the aggregation rates of lysozyme in the presence of the ammonium salts were smaller than the ones estimated from Tm. Comparing with sodium salts, ammonium salts increased the solubility of the hydrophobic amino acids, indicating that ammonium salts adsorb the hydrophobic region of proteins, which leads to the decrease in aggregation more effectively than sodium salts. The positive relation between aggregation rate and Tm was described by another factor such as the surface tension of salt solutions. Fourier transform infrared spectral analysis showed that the thermal aggregates were likely to form β-sheet in solutions that give high molar surface tension increment. These results suggest that protein aggregation is attributed to the surface free energy of the solution.

Keywords

Thermal aggregationlysozymeammoniumthermal stabilitysurface tension

Abbreviations

ATR

Attenuated total reflection

Tm

Midpoint temperature of thermal unfolding

UV

Ultraviolet

MSTI

Molar surface tension increment

Arg

Arginine

Phe

Phenylalanine

Ile

Isoleucine

Ser

Serine

Gly-Gly

Glycylglycine

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Atsushi Hirano
    • 1
  • Hiroyuki Hamada
    • 1
  • Tatsunori Okubo
    • 2
  • Takumi Noguchi
    • 2
  • Hiroki Higashibata
    • 3
  • Kentaro Shiraki
    • 1
  1. 1.Institute of Applied PhysicsUniversity of TsukubaTsukubaJapan
  2. 2.Institute of Material ScienceUniversity of TsukubaTsukubaJapan
  3. 3.Faculty of Life ScienceToyo UniversityItakura-machiJapan