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1.  A Reducing Milieu Renders Cofilin Insensitive to Phosphatidylinositol 4,5-Bisphosphate (PIP2) Inhibition* 
The Journal of Biological Chemistry  2013;288(41):29430-29439.
Background: Cofilin is a key molecule for actin dynamics whose activity can be locally inhibited by PIP2.
Results: Changes in the cofilin structure upon reduction render cofilin insensitive to PIP2 inhibition.
Conclusion: Local effects of PIP2 on cofilin activity are determined by the redox microenvironment.
Significance: We discovered a mechanism of spatio-microenvironmental control of actin dynamics by cofilin reduction at the plasma membrane.
Oxidative stress can lead to T cell hyporesponsiveness. A reducing micromilieu (e.g. provided by dendritic cells) can rescue T cells from such oxidant-induced dysfunction. However, the reducing effects on proteins leading to restored T cell activation remained unknown. One key molecule of T cell activation is the actin-remodeling protein cofilin, which is dephosphorylated on serine 3 upon T cell costimulation and has an essential role in formation of mature immune synapses between T cells and antigen-presenting cells. Cofilin is spatiotemporally regulated; at the plasma membrane, it can be inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2). Here, we show by NMR spectroscopy that a reducing milieu led to structural changes in the cofilin molecule predominantly located on the protein surface. They overlapped with the PIP2- but not actin-binding sites. Accordingly, reduction of cofilin had no effect on F-actin binding and depolymerization and did not influence the cofilin phosphorylation state. However, it did prevent inhibition of cofilin activity through PIP2. Therefore, a reducing milieu may generate an additional pool of active cofilin at the plasma membrane. Consistently, in-flow microscopy revealed increased actin dynamics in the immune synapse of untransformed human T cells under reducing conditions. Altogether, we introduce a novel mechanism of redox regulation: reduction of the actin-remodeling protein cofilin renders it insensitive to PIP2 inhibition, resulting in enhanced actin dynamics.
doi:10.1074/jbc.M113.479766
PMCID: PMC3795243  PMID: 24003227
Cofilin; Oxidation-Reduction; Phosphatidylinositol Signaling; Redox Regulation; T Cell
2.  Molecular dynamics simulations on aqueous two-phase systems - Single PEG-molecules in solution 
BMC Biophysics  2012;5:14.
Background
Molecular Dynamics (MD) simulations are a promising tool to generate molecular understanding of processes related to the purification of proteins. Polyethylene glycols (PEG) of various length are commonly used in the production and purification of proteins. The molecular mechanisms behind PEG driven precipitation, aqueous two-phase formation or the effects of PEGylation are however still poorly understood.
Results
In this paper, we ran MD simulations of single PEG molecules of variable length in explicitly simulated water. The resulting structures are in good agreement with experimentally determined 3D structures of PEG. The increase in surface hydrophobicity of PEG of longer chain length could be explained on an atomic scale. PEG-water interactions as well as aqueous two-phase formation in the presence of PO4 were found to be correlated to PEG surface hydrophobicity.
Conclusions
We were able to show that the taken MD simulation approach is capable of generating both structural data as well as molecule descriptors in agreement with experimental data. Thus, we are confident of having a good in silico representation of PEG.
doi:10.1186/2046-1682-5-14
PMCID: PMC3469337  PMID: 22873343

Results 1-2 (2)