Amyloid fibril formation by macrophage migration inhibitory factor
- Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne (Switzerland)
- North Shore Long Island Jewish Research Institute, 300 Community Drive, Manhasset, NY (United States)
- New York University, School of Medicine, Departments of Psychiatry and Pathology, 560 First Avenue, New York, NY (United States)
- Yale University School of Medicine, 300 Cedar Street, New Haven, CT (United States)
We demonstrate herein that human macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine expressed in the brain and not previously considered to be amyloidogenic, forms amyloid fibrils similar to those derived from the disease associated amyloidogenic proteins {beta}-amyloid and {alpha}-synuclein. Acid denaturing conditions were found to readily induce MIF to undergo amyloid fibril formation. MIF aggregates to form amyloid-like structures with a morphology that is highly dependent on pH. The mechanism of MIF amyloid formation was probed by electron microscopy, turbidity, Thioflavin T binding, circular dichroism spectroscopy, and analytical ultracentrifugation. The fibrillar structures formed by MIF bind Congo red and exhibit the characteristic green birefringence under polarized light. These results are consistent with the notion that amyloid fibril formation is not an exclusive property of a select group of amyloidogenic proteins, and contribute to a better understanding of the factors which govern protein conformational changes and amyloid fibril formation in vivo.
- OSTI ID:
- 20793223
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 338, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.10.040; PII: S0006-291X(05)02275-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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