Insights into the Effects of Cancer Associated Mutations at the UPF2 and ATP-Binding Sites of NMD Master Regulator: UPF1
Abstract
:1. Introduction
2. Results
2.1. Effects of Mutations on the UPF1 Protein Stability
2.2. Molecular Dynamics Simulations
2.2.1. UPF2 and AMPPNP Stabilizes the Wild-Type UPF1
2.2.2. Effects of Cancer Variants in the ATP-Binding Pocket of UPF1
2.2.3. CH-Domain Mutants Enhance UPF1-UPF2 Binding
2.2.4. Conformations of the Wild-Type and Mutant Systems
3. Discussion
4. Materials and Methods
4.1. System Setup
4.2. Residue Scanning/Site-Directed Mutagenesis
4.3. Molecular Dynamics Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
NMD | nonsense-mediated mRNA decay |
mRNAs | messenger RNAs |
PTCs | premature termination codons |
eRF1 | eukaryotic release factor 1 |
UPF1 | up frameshift 1 |
DHX34 | DEAH box polypeptide 34 |
SMG1C | suppressor with morphological effect on genitalia 1 complex |
EJC | exon junction complex |
CCR4 | carbon catabolite repressor protein 4 |
DCPC | decapping complex |
PNRC2 | pro-rich nuclear receptor co-activator 2 |
CH-domain | cysteine-histidine-rich domain |
SF1 | superfamily 1 |
nsSNPs | non-synonymous single nucleotide polymorphism |
MDS | molecular dynamics simulations |
MOE | Molecular Operating Environment |
WT | wild-type |
SPC | simple point charge |
PME | particle mesh Ewald |
MM-PBSA | molecular mechanics/Poisson-Boltzmann surface area |
PCA | principal component analysis |
P bodies | processing bodies |
TCGA | the cancer genome atlas |
RMSD | root mean square deviation |
RMSF | root mean square fluctuation |
Rg | radius of gyration |
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Kalathiya, U.; Padariya, M.; Pawlicka, K.; Verma, C.S.; Houston, D.; Hupp, T.R.; Alfaro, J.A. Insights into the Effects of Cancer Associated Mutations at the UPF2 and ATP-Binding Sites of NMD Master Regulator: UPF1. Int. J. Mol. Sci. 2019, 20, 5644. https://doi.org/10.3390/ijms20225644
Kalathiya U, Padariya M, Pawlicka K, Verma CS, Houston D, Hupp TR, Alfaro JA. Insights into the Effects of Cancer Associated Mutations at the UPF2 and ATP-Binding Sites of NMD Master Regulator: UPF1. International Journal of Molecular Sciences. 2019; 20(22):5644. https://doi.org/10.3390/ijms20225644
Chicago/Turabian StyleKalathiya, Umesh, Monikaben Padariya, Kamila Pawlicka, Chandra S. Verma, Douglas Houston, Ted R. Hupp, and Javier Antonio Alfaro. 2019. "Insights into the Effects of Cancer Associated Mutations at the UPF2 and ATP-Binding Sites of NMD Master Regulator: UPF1" International Journal of Molecular Sciences 20, no. 22: 5644. https://doi.org/10.3390/ijms20225644