title: Amyloid fibril formation by macrophage migration inhibitory factor.
abstract: 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.
authors.affiliation: Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland. hilal.lashuel@epfl.ch
authors.forename: Hilal A
authors.initials: HA
authors.lastname: Lashuel
authors.forename: Bayan
authors.initials: B
authors.lastname: Aljabari
authors.forename: Einar M
authors.initials: EM
authors.lastname: Sigurdsson
authors.forename: Christine N
authors.initials: CN
authors.lastname: Metz
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: David J E
authors.initials: DJ
authors.lastname: Callaway
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
mesh_terms: D000682:Amyloid / Q000138:chemical synthesis* / Q000648:ultrastructure*; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry*; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D008263:Macrophage Migration-Inhibitory Factors; D046912:Multiprotein Complexes