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bioRxiv · 10.1101/2023.02.14.528413

Probing the hierarchical dynamics of DNA-sperm nuclear transition protein complex through fuzzy interaction and mesoscale condensation

Xie, S.·Yue, C.·Ye, S.·Li, Z.
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Abstract

Nuclear transition protein TNP1 is a crucial player mediating histone-protamine exchange in condensing spermatids. A unique combination of intrinsic disorder and multivalent properties turns TNP1 into an ideal agent for orchestrating the formation of versatile TNP-DNA assembly and endows the protein with potent value for vaccine design. Despite its significance, the physicochemical property and the molecular mechanism taken by TNP1 for histone replacement and DNA condensation are still poorly understood. In this study, for the first time, we expressed and purified in vitro human TNP1. We investigated the hierarchical dynamics of TNP1: DNA interaction by combing computational simulations, biochemical assay, fluorescence imaging, and atomic force microscopy. We analyzed fuzzy interactions between TNP1 and DNA at the atomistic level and assessed the influence of TNP1 association on the electrostatic and mechanical properties of DNA. Furthermore, the alteration of the physicochemical properties of the TNP1-DNA complex modulates its molecular assembly and phase separation. Our study sets the foundation for understanding TNP1-mediated histone replacement and sheds light on the encapsulation of genetic material by TNP1 for vaccine development.

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Xie, S., Yue, C., Ye, S., Li, Z.. 2023-02-15. Probing the hierarchical dynamics of DNA-sperm nuclear transition protein complex through fuzzy interaction and mesoscale condensation. https://doi.org/10.1101/2023.02.14.528413

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