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Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
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Differences in the molecular structure of beta(2)-microglobulin between two morphologically different amyloid fibrils

Hirotsugu Hiramatsu1, Ming Lu, Koichi Matsuo

  • 1Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.

Biochemistry
|December 24, 2009
PubMed

Insights

Molecular differences in beta(2)-microglobulin amyloid fibrils explain distinct morphologies. Needle-like fibrils exhibit specific carboxyl group protonation, suggesting "hook"-like interactions stabilize their structure.

Area of Science:

  • Biochemistry
  • Biophysics
  • Structural Biology

Background:

  • Beta(2)-microglobulin forms amyloid fibrils implicated in diseases.
  • Amyloid fibrils can exhibit diverse morphologies, including needle-like (LS) and worm-like (WL).
  • Understanding the molecular basis of fibril morphology is crucial for disease mechanism insights.

Purpose of the Study:

  • To investigate the molecular structural differences between LS and WL beta(2)-microglobulin amyloid fibrils.
  • To correlate specific molecular features with observed fibril morphologies.
  • To elucidate the stabilizing forces contributing to different fibril structures.

Main Methods:

  • Infrared (IR) spectroscopy
  • Raman spectroscopy
  • Vacuum-ultraviolet circular dichroism (VUV-CD) spectroscopy

Main Results:

  • Both LS and WL fibrils showed comparable beta-sheet content (53% and 47%, respectively).
  • Distinct protonation states of carboxyl side chains were observed: deprotonated (COO-) in LS fibrils and protonated (COOH) in WL fibrils at pH 2.5.
  • The pK(a) of carboxyl groups was significantly lowered in LS fibrils, indicating specific interactions.

Conclusions:

  • Specific "hook"-like interactions, involving hydrogen bonding and salt bridges, stabilize the LS fibrils enthalpically.
  • Carboxyl group interactions likely dictate the spatial arrangement of beta-strands and beta-sheets, leading to needle-like morphology.
  • The absence of these specific interactions in WL fibrils results in entropic stabilization and flexible morphology.

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