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  Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics.

Melkova, K., Zapletal, V., Jansen, S., Nomilner, E., Zachrdla, M., Hritz, J., et al. (2018). Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics. Journal of Biological Chemistry, 293(34), 13297-13309. doi:10.1074/jbc.RA118.001769.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-148F-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-D684-6
Genre: Journal Article

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 Creators:
Melkova, K., Author
Zapletal, V., Author
Jansen, S., Author
Nomilner, E., Author
Zachrdla, M., Author
Hritz, J., Author
Novacek, J., Author
Zweckstetter, M.1, Author              
Jensen, M. R., Author
Blackledge, M., Author
Zidek, L., Author
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: microtubule-associated protein (MAP); nuclear magnetic resonance (NMR); small-angle X-ray scattering (SAXS); Tau protein (Tau); protein conformation NMR relaxation paramagnetic relaxation enhancement (PRE)
 Abstract: Microtubule-associated protein 2c (MAP2c) is a 49-kDa intrinsically disordered protein regulating the dynamics of microtubules in developing neurons. MAP2c differs from its sequence homologue Tau in the pattern and kinetics of phosphorylation by cAMP-dependent protein kinase (PKA). Moreover, the mechanisms through which MAP2c interacts with its binding partners and the conformational changes and dynamics associated with these interactions remain unclear. Here, we used NMR relaxation and paramagnetic relaxation enhancement techniques to determine the dynamics and long-range interactions within MAP2c. The relaxation rates revealed large differences in flexibility of individual regions of MAP2c, with the lowest flexibility observed in the known and proposed binding sites. Quantitative conformational analyses of chemical shifts, small-angle X-ray scattering (SAXS), and paramagnetic relaxation enhancement measurements disclosed that MAP2c regions interacting with important protein partners, including Fyn tyrosine kinase, plectin, and PKA, adopt specific conformations. High populations of polyproline II and α-helices were found in Fyn- and plectin-binding sites of MAP2c, respectively. The region binding the regulatory subunit of PKA consists of two helical motifs bridged by a more extended conformation. Of note, although MAP2c and Tau did not differ substantially in their conformations in regions of high sequence identity, we found that they differ significantly in long-range interactions, dynamics, and local conformation motifs in their N-terminal domains. These results highlight that the N-terminal regions of MAP2c provide important specificity to its regulatory roles and indicate a close relationship between MAP2c's biological functions and conformational behavior.

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Language(s): eng - English
 Dates: 2018-06-202018-08-24
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1074/jbc.RA118.001769
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Title: Journal of Biological Chemistry
Source Genre: Journal
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Pages: - Volume / Issue: 293 (34) Sequence Number: - Start / End Page: 13297 - 13309 Identifier: -