Informace o publikaci
Conformation and dynamics of intrinsically disordered microtubule associated protein 2c
| Autoři | |
|---|---|
| Rok publikování | 2018 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Microtubule associated protein 2c (MAP2c) regulates structure and dynamics (polymerization and degradation) of microtubules in developing neurons and other cells. MAP2c is a 49 kDa intrinsically disordered protein (IDP) consisting of several structural and functional regions. The N-terminal part contains two important regions: An N-terminal region with a high content of negatively charged amino acids and a proline-rich region. The former segment contains a binding site for the regulatory subunit of cAMP-dependent protein kinase (PKA) and proposed binding site for steroids, while the latter one contains several phosphorylation sites. The second important part of MAP2c is a highlyconserved C-terminal domain that binds to microtubules. In order to investigate relation between highly dynamic structural features of MAP2c and its functions, we studied dynamics of MAP2c using nuclear magnetic resonance (NMR) relaxation and performed quantitative conformational analysis of NMR chemical shifts, small angle X-ray scattering, and paramagnetic relaxation enhancement. Pools of possible chain conformations were generated by the program Flexible-Meccano, which builds consecutively a polypeptide chain. The ensemble of structures reproducing the experimental data was selected by the program ASTEROIDS which uses a genetic algorithm. We found out that the least flexible amino acids are involved in transient long-range contacts between the acidic N-terminal domain and the microtubule-binding domain and that more ordered regions correlate with the regions of known or proposed function. Our results thus indicate importance of the N-terminal regions for the specificity of regulatory roles of MAP2c and a close relation between biological functions and conformational behavior of this protein |
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