香港六合彩

XClose

MRC Prion Unit and Institute of Prion diseases

Menu

Laszlo Hosszu

LH Port

l.hosszu@prion.ucl.ac.uk

Tel: 020 7679 5097
Courtauld Building, Room 101

鈥� 鈥�

听听

Research Synopsis

NMR spectroscopy is a unique method of studying proteins at the atomic level in solution, allowing us to determine their structure, function, and how they fold and unfold from their normal biological state. Understanding this is of major biomedical importance as a number of neurodegenerative diseases, such as Alzheimer鈥檚, Parkinson's and the prion diseases, CJD and BSE, involve protein misfolding and partially and misfolded protein states. We have shown how NMR can be used to determine structural and dynamic information of such states, which provide a basis for identifying where and how to interrupt amyloidogenesis before the onset of neurodegeneration.

Recent highlights include the structure determination and biophysical characterisation of the disease-resistant form of prion protein, V127, in its normal cellular fold. Key regions of the protein which are associated with the development of prion diseases were identified, providing insights into its protective mechanism, and how prion protein misfolding is involved.

LH Fig

Structural variability in V127 prion protein

听

Selected Publications

Structural perturbations induced by protective V127 mutation in cellular prion protein
Hosszu LLP, Conners R, Sangar D, Batchelor M..... McAuley K, Brady RL, Bieschke J, Waltho JP, Collinge J (2018)


Kenny J, Woollacott I, Koriath C, Hosszu LLP, Adamson G, Rudge P..... Mead S, (2017) . J. Neurology, Neurosurgery, & Psychiatry, 88, 890-892


Terry C, Wenborn A, Gros N, Sells J, Joiner S, Hosszu LLP..... Wadsworth JD (2016) . Open Biology, 6, 160035


Trevitt CR, Hosszu LLP, Batchelor M, Panico S, Terry C..... Collinge J, Waltho JP, Clarke AR (2014) Journal of Biological Chemistry 289, 25497-508


Hosszu LLP, Tattum MH, Jones S, Trevitt CR, Wells MA, Waltho JP, Collinge J... Clarke AR (2010) Biochemistry, 49, 8729-38


Hart T, Hosszu LLP, Trevitt CR, Jackson GS, Waltho JP, Collinge J, Clarke AR (2009). Proc. Natl. Acad. Sci .USA, 106, 5651-6


Jackson GS, Murray I, Hosszu LLP, Gibbs N, Waltho JP, Clarke AR, Collinge J (2001) Proc. Natl. Acad. Sci .USA. 98, 8531-5


Hosszu LLP, Baxter NJ, Jackson GS, Power A, Clarke AR, Waltho JP, Craven CJ, Collinge J (1999) . Nat. Struct. Biol. 6, 740-3
听