MELKOVÁ, Kateřina, Vojtěch ZAPLETAL, Séverine JANSEN, Erik NOMILNER, Milan ZACHRDLA, Jozef HRITZ, Jiří NOVÁČEK, M. ZWECKSTETTER, M.R. JENSEN, M. BLACKLEDGE and Lukáš ŽÍDEK. Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics. The Journal of Biological Chemistry. Bethesda, USA: American Society for Biochemistry and Molecular Biology, vol. 293, No 34, p. 13297-13309. ISSN 0021-9258. 2018.
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Basic information
Original name Functionally specific binding regions of microtubule-associated protein 2c exhibit distinct conformations and dynamics
Authors MELKOVÁ, Kateřina (203 Czech Republic, belonging to the institution), Vojtěch ZAPLETAL (203 Czech Republic, belonging to the institution), Séverine JANSEN (250 France, belonging to the institution), Erik NOMILNER (703 Slovakia, belonging to the institution), Milan ZACHRDLA (203 Czech Republic, belonging to the institution), Jozef HRITZ (703 Slovakia, belonging to the institution), Jiří NOVÁČEK (203 Czech Republic, belonging to the institution), M. ZWECKSTETTER (276 Germany), M.R. JENSEN (250 France), M. BLACKLEDGE (250 France) and Lukáš ŽÍDEK (203 Czech Republic, guarantor, belonging to the institution).
Edition The Journal of Biological Chemistry, Bethesda, USA, American Society for Biochemistry and Molecular Biology, 2018, 0021-9258.
Other information
Original language English
Type of outcome Article in a journal
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
RIV identification code RIV/00216224:14740/18:00101098
Organization Středoevropský technologický institut – Repository – Repository
UT WoS 000442730200027
Keywords in English NMR relaxation; Tau protein (Tau); microtubule-associated protein (MAP); nuclear magnetic resonance (NMR); paramagnetic relaxation enhancement (PRE); protein conformation; small-angle X-ray scattering (SAXS)
Links EF16_013/0001776, research and development project. GA15-14974S, research and development project. LM2015043, research and development project. LM2015085, research and development project. 692068, interní kód Repo.
Changed by Changed by: RNDr. Daniel Jakubík, učo 139797. Changed: 6/9/2020 03:28.
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 alpha-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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  • a concrete person Mgr. Lucie Vařechová, uco 106253
  • a concrete person RNDr. Daniel Jakubík, uco 139797
  • a concrete person Mgr. Jolana Surýnková, uco 220973
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