ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P132. Transferrin Fibrillation and Iron Nanomineralization
A. Mukherjee a , S. Ghosh b , M. A. Barnett c , J. P. Willaims a , N. Wilson d , P. J. Sadler a ,
S. Verma b
a
Department of Chemistry, University of Warwick, Gibbett Hill Road, CV47AL, Coventry, United Kingdom,
b
Chemistry, Indian Institute of technology Kanpur, Kanpur, India
c
Research Support Services, University of Warwick, Department of Chemistry, CV47AL, Coventry, United
Kingdom
d
Physics, University of Warwick, Gibbett Hill Road, CV47AL, Coventry, United Kingdom
e-mail: arindam.mukherjee@warwick.ac.uk
Aggregation of extracelluar proteins and peptides such as prion protein, alpha-synuclein, insulin, beta2microglobulin
and amyloid beta- peptide is found in patients with various neurodegenerative diseases, e.g.
Alzheimer’s, Parkinson’s and Halloverden-spatz disease [1]. Fe, Mn, Cu are known to induce oxidative stress,
and in addition abnormal iron deposits are found in the brains of dementia patients. We are investigating the
possibility that human serum transferrin (hTf), an extracellular Fe(III)-transporting glycoprotein [2] present in
blood and in brain could play a role in iron deposition. Using various types of microscopy (TEM, AFM, SEM),
we have found that human serum transferrin readily forms fibres, typically 200-300 nm wide, on various
surfaces (e.g. carbon, formvar, mica)[3]. Fibrillation is observed with apo-, holo-, Mn2III-hTf, Bi2III-hTf and
holo deglycosylated hTf. Thus the glycan chains and the metal appear to have little or no role in fibril formation.
Periodic iron nanomineralization was observed in fibrils of holo-hTf. TEM experiments show that fibrils can
form under physiologically relevant conditions. Mass spectrometry shows that transferrin can form dimers and
trimers in the gas phase. Other proteins from the same family such as lactoferrin and ovo-transferrin also
undergo fibrillation on carbon-coated formvar surfaces.
References:
[1] A. Khan, J.P. Dobson, C. Exley, Free Rad. Biol. Med. 2006, 40, 557.
[2] H. Sun, H. Li and P.J. Sadler, Chem. Rev. 1999, 99, 2817.
[3] S.Ghosh, A. Mukherjee, P.J. Sadler, S. Verma, Angew. Chem. Int. Ed. 2008, 47, 2217.
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