Structural Mechanism behind Distinct Efficiency of Oct4/Sox2 Proteins in Differentially Spaced DNA Complexes

PloS One
Dhanusha YesudhasSangdun Choi

Abstract

The octamer-binding transcription factor 4 (Oct4) and sex-determining region Y (SRY)-box 2 (Sox2) proteins induce various transcriptional regulators to maintain cellular pluripotency. Most Oct4/Sox2 complexes have either 0 base pairs (Oct4/Sox2(0bp)) or 3 base pairs (Oct4/Sox2(3bp)) separation between their DNA-binding sites. Results from previous biochemical studies have shown that the complexes separated by 0 base pairs are associated with a higher pluripotency rate than those separated by 3 base pairs. Here, we performed molecular dynamics (MD) simulations and calculations to determine the binding free energy and per-residue free energy for the Oct4/Sox2(0bp) and Oct4/Sox2(3bp) complexes to identify structural differences that contribute to differences in induction rate. Our MD simulation results showed substantial differences in Oct4/Sox2 domain movements, as well as secondary-structure changes in the Oct4 linker region, suggesting a potential reason underlying the distinct efficiencies of these complexes during reprogramming. Moreover, we identified key residues and hydrogen bonds that potentially facilitate protein-protein and protein-DNA interactions, in agreement with previous experimental findings. Consequently, our re...Continue Reading

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Citations

May 28, 2019·Journal of Cellular Biochemistry·Wen-Shan LiuRun-Ling Wang
Apr 14, 2021·The Journal of Physical Chemistry. B·Reman Kumar Singh, Arnab Mukherjee

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Methods Mentioned

BETA
PCA

Software Mentioned

Visual Molecular Dynamics
UCSF Chimera
CentOS6
Dock Prep application
AMBERTools
Matplotlib PowerEdge
MMPBSA
GROMACS
TIFF
AMBER

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