Fibrillation of transferrin

Claire Booyjz̈sen, Charlotte A. Scarff, Ben Moreton, Ian Portman, James Scrivens, Giovanni Costantini, Peter J. Sadler

    Research output: Contribution to journalReview articlepeer-review

    5 Citations (Scopus)

    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. Methods and 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. 250 nm in diameter. Small transferrin fibrils ca. 250 nm 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. General significance: 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.

    Original languageEnglish
    Pages (from-to)427-436
    Number of pages10
    JournalBiochimica et Biophysica Acta - General Subjects
    Volume1820
    Issue number3
    DOIs
    Publication statusPublished - 1 Mar 2012

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