XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta
XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta
XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Lectures<br />
StrUCTUral anaLYSIS of tau prOTEIN, THE CONSTITUENT of<br />
NEUrofIBrILLary paTHOLOGY IN aLZHEIMEr’s DISEaSE<br />
Rostislav Skrabana 1,2 , Radovan Dvorsky 3 , Branislav Kovacech 1,2 ,<br />
Zuzana Flachbartova 1 , Ondrej Cehlar 1 , Jozef Sevcik 4 and Michal Novak 1,2<br />
1<br />
Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia;<br />
2<br />
Axon Neuroscience GmbH, Vienna, Austria; 3 Max Planck Institute for Molecular<br />
Physiology, Dortmund, Germany; 4 Institute of Molecular Biology, Slovak Academy<br />
of Sciences, Bratislava, Slovakia<br />
Neuronal protein tau is one of the prominent microtubule-associated proteins in the<br />
brain. Tau shows typical features of an intrinsically disordered protein including low sequence<br />
complexity and large proportion of polar and charged amino acids. Tau protein<br />
amino acid composition implicates a high net charge at physiologic pH and a low mean<br />
hydrophobicity, increased hydrodynamic volume and a negligible content of secondary<br />
structure. Tau protein has an important role for the development of axons; on the other<br />
hand it is implicated in misfolded paired helical filaments (PHF) occurring in Alzheimer’s<br />
disease and other tauopathies. Traditionally, tau protein flexibility posed substantial<br />
limitations for assessing its structure using spectroscopic and/or diffraction techniques.<br />
However, recent technology advancements allowed deeper insight into tau protein<br />
conformational freedom. Using monoclonal antibodies as surrogate tau binding partners<br />
it was possible to stabilize a distinct tau protein conformation which can be studied by<br />
X-ray crystallography. Monoclonal antibody MN423, which recognizes a conformation<br />
of tau protein assembled into Alzheimer PHF core could be used as a molecular mould<br />
for studying PHF fold using disordered molecule of recombinant tau and adopting X-ray<br />
crystallography, biophysical techniques and molecular dynamics methods. Similarly,<br />
other antibodies directed against distinct parts of tau protein molecule, provided data<br />
about conformational space of tau.<br />
Acknowledgement: This work was supported by the Slovak Research and Development<br />
Agency under the contracts Nos. APVV-0471-06, APVV-0634-07, LPP-0038-09, by the<br />
Slovak Grant Agency VEGA grants Nos. 2/6172/26, 2/0162/10, 2/0217/10 and by the<br />
International Centre for Genetic Engineering and Biotechnology grant No. CRP/SVK05-01.<br />
<strong>XXII</strong>. Biochemistry Congress, Martin<br />
95