XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
StrUCTUral anaLYSIS of tau prOTEIN, THE CONSTITUENT of
NEUrofIBrILLary paTHOLOGY IN aLZHEIMEr’s DISEaSE
Rostislav Skrabana 1,2 , Radovan Dvorsky 3 , Branislav Kovacech 1,2 ,
Zuzana Flachbartova 1 , Ondrej Cehlar 1 , Jozef Sevcik 4 and Michal Novak 1,2
1
Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia;
2
Axon Neuroscience GmbH, Vienna, Austria; 3 Max Planck Institute for Molecular
Physiology, Dortmund, Germany; 4 Institute of Molecular Biology, Slovak Academy
of Sciences, Bratislava, Slovakia
Neuronal protein tau is one of the prominent microtubule-associated proteins in the
brain. Tau shows typical features of an intrinsically disordered protein including low sequence
complexity and large proportion of polar and charged amino acids. Tau protein
amino acid composition implicates a high net charge at physiologic pH and a low mean
hydrophobicity, increased hydrodynamic volume and a negligible content of secondary
structure. Tau protein has an important role for the development of axons; on the other
hand it is implicated in misfolded paired helical filaments (PHF) occurring in Alzheimer’s
disease and other tauopathies. Traditionally, tau protein flexibility posed substantial
limitations for assessing its structure using spectroscopic and/or diffraction techniques.
However, recent technology advancements allowed deeper insight into tau protein
conformational freedom. Using monoclonal antibodies as surrogate tau binding partners
it was possible to stabilize a distinct tau protein conformation which can be studied by
X-ray crystallography. Monoclonal antibody MN423, which recognizes a conformation
of tau protein assembled into Alzheimer PHF core could be used as a molecular mould
for studying PHF fold using disordered molecule of recombinant tau and adopting X-ray
crystallography, biophysical techniques and molecular dynamics methods. Similarly,
other antibodies directed against distinct parts of tau protein molecule, provided data
about conformational space of tau.
Acknowledgement: This work was supported by the Slovak Research and Development
Agency under the contracts Nos. APVV-0471-06, APVV-0634-07, LPP-0038-09, by the
Slovak Grant Agency VEGA grants Nos. 2/6172/26, 2/0162/10, 2/0217/10 and by the
International Centre for Genetic Engineering and Biotechnology grant No. CRP/SVK05-01.
XXII. Biochemistry Congress, Martin
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