Study of domain interactions of intrinsically disordered protein MAP2c (Microtubule-Associated Protein 2c) with its binding partners via computational methods and nuclear magnetic resonance
Project goals
The main focus of this project is MAP2c (Microtubule-Associated Protein 2c) protein, an IDP regulating structure and dynamics (polymerization and degradation) of microtubules (MTs) which is essential for correct function of cytoskeleton of nervous and other cells (intracellular transport, cell replication and growth). MAP2c is a 49 kDa protein consisting of several structural and functional regions. The N-terminal part contains two important regions: The N-terminus itself with a high content of negatively charged amino acids and the region rich in proline. This segment contains a probable binding site for other regulatory proteins that interact with MAP2c, such as the SH3 domain of plectin. The second important part of MAP2c is a highly conserved C-terminal domain that binds to MTs. The aim of this project is to follow up on our preliminary results using methods developed in the principal investigator’s group and to describe experimentally the so far insufficiently explored properties of the MAP2c domains and their influence on the protein function and interaction with potential interaction partners. To obtain a relevant model describing structural and interaction characteristics of the studied molecule we propose performing molecular dynamics simulations for individual MAP2c regions and using the results for interpretation of the NMR data on the level of representative conformational ensembles.
Keywords
Intrinsically disordered proteinsnuclear magnetic resonancemolecular dynamics
Public support
Provider
Ministry of Education, Youth and Sports
Programme
INTER-EXCELLENCE
Call for proposals
INTER-EXCELLENCE 2 (SMSM2016LTC01)
Main participants
Masarykova univerzita / Středoevropský technologický institut
Contest type
VS - Public tender
Contract ID
MSMT-15304/2017-1
Alternative language
Project name in Czech
Studium interakcí domén přirozeně neuspořádaného proteinu MAP2c (microtubule- associated protein 2c) s jeho vazebnými partnery pomocí výpočetních metod a nukleární magnetické rezonance
Annotation in Czech
Cílem projektu je experimentálně popsat dosud nedostatečně prozkoumané vlastnosti domén, a vliv jednotlivých regionů MAP2c na funkci celého proteinu či na interakci s případnými vazebnými partnery, čehož chceme dosáhnout kombinací výpočetních a experimentálních metod. Jelikož cílovou molekulou je přirozeně neuspořádané protein strukturně i funkčně spojovaný s rozvojem neurodegenerativních chorob, je projekt atraktivní i z hlediska lékařského využití a výsledná publikace může posloužit pro další specifičtější výzkum.
Scientific branches
Completed project evaluation
Provider evaluation
V - Vynikající výsledky projektu (s mezinárodním významem atd.)
Project results evaluation
Based on analysis of NMR parameters, we characterized transient structures of protein Tau and compared them with the results of the MAP2c analysis. We revealed large differences in N-terminal regions and important deviations in C-terminal parts. We compared results for both proteins with their interactions, physiological, and pathological functions, and published them in the journal Biomolecules
Solution timeline
Realization period - beginning
Jun 1, 2017
Realization period - end
Mar 25, 2019
Project status
U - Finished project
Latest support payment
Feb 25, 2019
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP20-MSM-LT-U/01:3
Data delivery date
Jun 19, 2020
Finance
Total approved costs
1,425 thou. CZK
Public financial support
1,425 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK
Basic information
Recognised costs
1 425 CZK thou.
Public support
1 425 CZK thou.
100%
Provider
Ministry of Education, Youth and Sports
CEP
CE - Biochemistry
Solution period
01. 06. 2017 - 25. 03. 2019