Structure analysis of disease-related proteins using vibrational spectroscopy

Hirotsugu Hiramatsu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Analyses of the structure and properties of identified pathogenic proteins are important for elucidating the molecular basis of diseases and in drug discovery research. Vibrational spectroscopy has advantages over other techniques in terms of sensitivity of detection of structural changes. Spectral analysis, however, is complicated because the spectrum involves a substantial amount of information. This article includes examples of structural analysis of disease-related proteins using vibrational spectroscopy in combination with additional techniques that facilitate data acquisition and analysis. Residue-specific conformation analysis of an amyloid fibril was conducted using IR absorption spectroscopy in combination with13C-isotope labeling, linear dichroism measurement, andanalysisofamide Ibandfeatures. We reveal a pH-dependent property of the interacting segment of an amyloidogenic protein, β2-microglobulin, which causes dialysis-related amyloidosis. We also reveal the molecular mechanisms underlying pH-dependent sugar-binding activity of human galectin-1, which is involved in cell adhesion, using spectroscopic techniques including UV resonance Raman spectroscopy. The decreased activity at acidic pH was attributed to a conformational change in the sugar-binding pocket caused by protonation of His52 (pKa 6.3) and the cation-π interaction between Trp68 and the protonated His44 (pKa 5.7). In addition, we show that the peak positions of the Raman bands of the C4=C5 stretching mode at approximately 1600 cm-1 and the Nπ-C2-Nτ bending mode at approximately 1405 cm-1 serve as markers of the His side-chain structure. The Raman signal was enhanced 12 fold using a vertical flow apparatus.

Original languageEnglish
Pages (from-to)1013-1020
Number of pages8
JournalYakugaku Zasshi
Volume134
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

Keywords

  • Disease-related protein
  • Raman marker band
  • Residue-specific analysis
  • Signal-to-noise ratio
  • Vibrational spectroscopy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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