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Biomolecules. 2019 Mar 16;9(3). pii: E105. doi: 10.3390/biom9030105.

Structure and Functions of Microtubule Associated Proteins Tau and MAP2c: Similarities and Differences.

Author information

1
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. katerina.melkova@ceitec.muni.cz.
2
Faculty of Science, National Centre for Biomolecular Research, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. katerina.melkova@ceitec.muni.cz.
3
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. vojtech.zapletal@ceitec.muni.cz.
4
Faculty of Science, National Centre for Biomolecular Research, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. vojtech.zapletal@ceitec.muni.cz.
5
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. subhash.narasimhan@ceitec.muni.cz.
6
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. severine@chemi.muni.cz.
7
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. jozef.hritz@ceitec.muni.cz.
8
Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 10 Bratislava, Slovakia. rostislav.skrabana@savba.sk.
9
Axon Neuroscience R&D Services SE, Dvořákovo nábrežie 10, 811 02 Bratislava, Slovakia. rostislav.skrabana@savba.sk.
10
German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 Göttingen, Germany. Markus.Zweckstetter@dzne.de.
11
Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Markus.Zweckstetter@dzne.de.
12
University Grenoble Alps, CEA, CNRS, 38000 Grenoble, France. malene.ringkjobing-jensen@ibs.fr.
13
University Grenoble Alps, CEA, CNRS, 38000 Grenoble, France. martin.blackledge@ibs.fr.
14
Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. lzidek@chemi.muni.cz.
15
Faculty of Science, National Centre for Biomolecular Research, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. lzidek@chemi.muni.cz.

Abstract

The stability and dynamics of cytoskeleton in brain nerve cells are regulated by microtubule associated proteins (MAPs), tau and MAP2. Both proteins are intrinsically disordered and involved in multiple molecular interactions important for normal physiology and pathology of chronic neurodegenerative diseases. Nuclear magnetic resonance and cryo-electron microscopy recently revealed propensities of MAPs to form transient local structures and long-range contacts in the free state, and conformations adopted in complexes with microtubules and filamentous actin, as well as in pathological aggregates. In this paper, we compare the longest, 441-residue brain isoform of tau (tau40), and a 467-residue isoform of MAP2, known as MAP2c. For both molecules, we present transient structural motifs revealed by conformational analysis of experimental data obtained for free soluble forms of the proteins. We show that many of the short sequence motifs that exhibit transient structural features are linked to functional properties, manifested by specific interactions. The transient structural motifs can be therefore classified as molecular recognition elements of tau40 and MAP2c. Their interactions are further regulated by post-translational modifications, in particular phosphorylation. The structure-function analysis also explains differences between biological activities of tau40 and MAP2c.

KEYWORDS:

intrinsically disordered protein; microtubule associated protein; nuclear magnetic resonance; phosphorylation; tau

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