Imperial College London
Portrait Picture

ProfessorIanGould

Faculty of Natural Sciences, Department of Chemistry

Senior Research Investigator
 
 
 
//

Contact

 

+44 (0)20 7594 5809i.gould

 
 
//

Location

 

110BMolecular Sciences Research HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Zamora:2016:10.1039/c6cp02610a,
author = {Zamora, JE and Papadaki, M and Messer, AE and Marston, SB and Gould, IR},
doi = {10.1039/c6cp02610a},
journal = {Physical Chemistry Chemical Physics},
pages = {20691--20707},
title = {Troponin structure: its modulation by Ca(2+) and phosphorylation studied by molecular dynamics simulations.},
url = {http://dx.doi.org/10.1039/c6cp02610a},
volume = {18},
year = {2016}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The only available crystal structure of the human cardiac troponin molecule (cTn) in the Ca(2+) activated state does not include crucial segments, including the N-terminus of the cTn inhibitory subunit (cTnI). We have applied all-atom molecular dynamics (MD) simulations to study the structure and dynamics of cTn, both in the unphosphorylated and bis-phosphorylated states at Ser23/Ser24 of cTnI. We performed multiple microsecond MD simulations of wild type (WT) cTn (6, 5 μs) and bisphosphorylated (SP23/SP24) cTn (9 μs) on a 419 amino acid cTn model containing human sequence cTnC (1-161), cTnI (1-171) and cTnT (212-298), including residues not present in the crystal structure. We have compared our results to previous computational studies, and proven that longer simulations and a water box of at least 25 Å are needed to sample the interesting conformational shifts both in the native and bis-phosphorylated states. As a consequence of the introduction into the model of the C-terminus of cTnT that was missing in previous studies, cTnC-cTnI interactions that are responsible for the cTn dynamics are altered. We have also shown that phosphorylation does not increase cTn fluctuations, and its effects on the protein-protein interaction profiles cannot be assessed in a significant way. Finally, we propose that phosphorylation could provoke a loss of Ca(2+) by stabilizing out-of-coordination distances of the cTnC's EF hand II residues, and in particular Ser 69.
AU  - Zamora,JE
AU  - Papadaki,M
AU  - Messer,AE
AU  - Marston,SB
AU  - Gould,IR
DO  - 10.1039/c6cp02610a
EP  - 20707
PY  - 2016///
SN  - 1463-9084
SP  - 20691
TI  - Troponin structure: its modulation by Ca(2+) and phosphorylation studied by molecular dynamics simulations.
T2  - Physical Chemistry Chemical Physics
UR  - http://dx.doi.org/10.1039/c6cp02610a
VL  - 18
ER  -
Download