Microtubule Associated Protein 2c interacts with multiple partners at specific sites

Jitka Plucarová1,2,  Subhash Narasimhan1,2, Kateřina Bendová1,2, Erik Nomilner1,2,  Séverine Jansen1, Jozef Hritz1,2, Lukáš Žídek1,2,

1Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic

2Faculty of Science, National Center for Biomolecular Research, Kamenice 5, 625 00 Brno, Czech Republic

lzidek@chemi.muni.cz

The Microtubule Associated Proteins (MAPs) regulate the stability and the dynamics of the cytoskeleton.  The main structural MAPs, tau and MAP2, are expressed in neurones and are involved in neurodegenerative diseases, such as Alzheimer's disease. Tau and MAP2 are both intrinsically disordered proteins, lacking a fixed three-dimensional structure. However, nuclear magnetic resonance revealed propensities of MAPs to form transient local structures and long-range contacts in the free state [1, 2].  MAP2c, the juvenile MAP2, is expressed during brain development. In addition to its role in the control of dynamics of microtubules and actin filaments, MAP2c is involved in interactions with multiple proteins or small ligands,  implied in neuronal development, in the regulation of the cytoskeleton plasticity, or anchoring the cytoskeleton to organelles.

Here, we present the interaction of MAP2c with different proteins, such as 14-3-3 [3], the cytolinker plectin and the RII regulatory subunit of PKA, as well as with neurosteroids. Interestingly, the sites of interaction with the different proteins can be linked to transient structural features observed in free MAP2c [1, 2].

1. K. Melková, V. Zapletal, S. Jansen, E. Nomilner, M. Zachrdla, J. Hritz, J. Nováček, M. Zweckstetter,  M.  R. Jensen, M. Blackledge, L. Žídek, J. Biol. Chem., 293, (2018), 13297–13309

2. K. Melková, V. Zapletal, S. Narasimhan, S. Jansen, J. Hritz, R. Škrabana, M. Zweckstetter, M. Ringkjøbing Jensen, M. Blackledge, L. Žídek, Biomolecules, 9, (2019), 105

3. S. Jansen, K. Melková, Z. Trošanová, K. Hanáková, M. Zachrdla, J. Nováček, E. Župa, Z. Zdráhal, J. Hritz, L. Žídek,  J. Biol. Chem., 292, (2017), 6715–6727

This study was supported by the Czech Science Foundation (grant 20-12669S) and CIISB research infrastructure project LM2018127 funded by MEYS CR is gratefully acknowledged for the financial support of the measurements at the Josef Dadok National NMR Centre.