@article {49337,
	title = {DNA-mediated formation of phase-separated coacervates of the nucleic acid-binding domain of TAR DNA-binding protein (TDP-43) prevents its amyloid-like misfolding},
	journal = {ACS Chemical Neuroscience},
	volume = {15},
	year = {2024},
	month = {OCT },
	pages = {4105-4122},
	type = {Article},
	abstract = {<p>
	Sequestration of protein molecules and nucleic acids to stress granules is one of the most promising strategies that cells employ to protect themselves from stress. In vitro, studies suggest that the nucleic acid-binding domain of TDP-43 (TDP-43tRRM) undergoes amyloid-like aggregation to beta-sheet-rich structures in low pH stress. In contrast, we observed that the TDP-43tRRM undergoes complex coacervation in the presence of ssDNA to a dense and light phase, preventing its amyloid-like aggregation. The soluble light phase consists of monomeric native-like TDP-43tRRM. The microscopic data suggest that the dense phase consists of spherical coacervates with limited internal dynamics. We performed multiparametric analysis by employing various biophysical techniques and found that complex coacervation depends on the concentration and ratio of the participating biomolecules and is driven by multivalent interactions. The modulation of these forces due to environmental conditions or disease mutations regulates the extent of coacervation, and the weakening of interactions between TDP-43tRRM and ssDNA leads to amyloid-like aggregation of TDP-43tRRM. Our results highlight a competition among the native state, amyloid-like aggregates, and complex coacervates tuned by various environmental factors. Together, our results illuminate an alternate function of TDP-43tRRM in response to pH stress in the presence of the ssDNA.</p>
},
	keywords = {amyloid-likeaggregation, complex coacervation, DNA-protein interactions, Dynamics, pH stress, TDP-43},
	issn = {1948-7193},
	doi = {10.1021/acschemneuro.4c00117},
	author = {Patni, Divya and Patil, Anjali D. and Kirmire, Mona S. and Jha, Anjali and Jha, Santosh Kumar}
}
@article {49414,
	title = {Molecular interactions of the pioneer transcription factor GATA3 With DNA},
	journal = {Proteins-Structure Function and Bioinformatics},
	volume = {93},
	year = {2025},
	month = {FEB},
	pages = {555-566},
	type = {Article},
	abstract = {<p>
	The GATA3 transcription factor is a pioneer transcription factor that is critical in the development, proliferation, and maintenance of several immune cell types. Identifying the detailed conformational dynamics and interactions of this transcription factor, as well as its clinically important population variants will allow us to unravel its mode of action. In this study, we analyze the molecular interactions of the GATA3 transcription factor bound to dsDNA as well as three clinically important population variants by atomistic molecular dynamics simulations. We identify the effect of the variants on the DNA conformational dynamics and delineate the differences compared to the wildtype transcription factor that could be related to impaired function. We highlight the structural plasticity in the binding of the GATA3 transcription factor and identify important DNA-protein contacts. Although the DNA-protein contacts are persistent and appear to be stable, they exhibit nanosecond timescale fluctuations and several binding/unbinding events. Further, we identify differential DNA binding in the three variants and show that the N-terminal binding is reduced in two of the variants. Our results indicate that reduced minor groove width and DNA diameter are important hallmarks for the binding of GATA3. Our work is an important step towards understanding the functional dynamics of the GATA3 protein and its clinically significant population variants.</p>
},
	keywords = {DNA-protein interactions, GATA protein, Molecular dynamics simulations, molecular mechanism, population variants, transcription factor},
	issn = {0887-3585},
	doi = {10.1002/prot.26749},
	author = {Gharui, Sowmomita and Sengupta, Durba}
}
