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Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
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
Summary
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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