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Amyloid fibril formation by macrophage migration inhibitory factor
Hilal A Lashuel1, Bayan Aljabari, Einar M Sigurdsson
1Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland. hilal.lashuel@epfl.ch
Biochemical and Biophysical Research Communications
|November 16, 2005
Summary
Human macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, can form amyloid fibrils under acidic conditions. This finding expands our understanding of amyloid formation beyond traditionally amyloidogenic proteins.
Area of Science:
- Biochemistry
- Neuroscience
- Protein Chemistry
Background:
- Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine found in the brain.
- MIF was not previously considered to be amyloidogenic.
- Amyloid fibrils are associated with neurodegenerative diseases.
Purpose of the Study:
- To investigate the amyloidogenic potential of human MIF.
- To characterize the amyloid fibrils formed by MIF.
- To understand the factors governing MIF amyloid formation.
Main Methods:
- Acid denaturation to induce fibril formation.
- Electron microscopy for structural analysis.
- Turbidity, Thioflavin T binding, and circular dichroism spectroscopy to probe the mechanism.
- Analytical ultracentrifugation for aggregate characterization.
- Congo red binding and polarized light microscopy to confirm amyloid properties.
Main Results:
- Human MIF readily forms amyloid fibrils under acidic denaturing conditions.
- MIF fibril morphology is pH-dependent.
- The formed fibrils exhibit characteristic amyloid properties, including Congo red binding and green birefringence.
- These findings suggest that amyloid formation is not exclusive to known amyloidogenic proteins.
Conclusions:
- MIF is capable of forming amyloid fibrils, challenging previous assumptions.
- Protein conformational changes and amyloid fibril formation can occur under various conditions, not limited to specific proteins.
- This study contributes to understanding the broader mechanisms of protein aggregation and amyloidogenesis in vivo.
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