title: Fibrillation of transferrin.
abstract: BACKGROUND
  The nature of fibrillar deposits from aqueous solutions of human serum and recombinant human transferrin on mica and carbon-coated formvar surfaces has been investigated.
  
  
  RESULTS
  Atomic force microscopy showed that the deposition of recombinant transferrin onto the hydrophilic surface of mica resulted in the formation of a monolayer-thick film composed of conformationally-strained flattened protein molecules. Elongated fibres developed on top of this layer and appeared to be composed of single proteins or small clusters thereof. Monomeric and dimeric transferrins were separated by gel permeation chromatography and their states of aggregation confirmed by mass spectrometry and dynamic light scattering. Transmission electron-microscopy showed that dimeric transferrin, but not monomeric transferrin, deposited on carbon-coated formvar grids forms rounded (circular) structures ca. 250nm in diameter. Small transferrin fibrils ca. 250nm long appeared to be composed of smaller rounded sub-units. Synchrotron radiation-circular dichroism and, Congo red and thioflavin-T dye-binding experiments suggested that transferrin aggregation in solution does not involve major structural changes to the protein or formation of classical β-sheet amyloid structures. Collisional cross sections determined via ion mobility-mass spectrometry showed little difference between the overall protein shapes of apo- and holo-transferrin in the gas phase.
  
  
  CONCLUSIONS
  The possibility that transferrin deformation and aggregation are involved in neurological disorders such as Parkinson's and Alzheimer's disease is discussed. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.
authors: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors: Claire
authors: C
authors: Booyjzsen
authors: Charlotte A
authors: CA
authors: Scarff
authors: Ben
authors: B
authors: Moreton
authors: Ian
authors: I
authors: Portman
authors: James H
authors: JH
authors: Scrivens
authors: Giovanni
authors: G
authors: Costantini
authors: Peter J
authors: PJ
authors: Sadler
mesh_terms: D001665:Binding Sites; D003460:Crystallization; D006801:Humans; D007501:Iron / Q000378:metabolism; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D014168:Transferrin; D007501:Iron