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Halogenation of tyrosine perturbs large-scale protein self-organization

Sun, Huan; Jia, Haiyang; Kendall, Olivia; Dragelj, Jovan; Kubyshkin, Vladimir; Baumann, Tobias; Mroginski, Maria-Andrea; Schwille, Petra; Budisa, Nediljko

Protein halogenation is a common non-enzymatic post-translational modification contributing to aging, oxidative stress-related diseases and cancer. Here, we report a genetically encodable halogenation of tyrosine residues in a reconstituted prokaryotic filamentous cell-division protein (FtsZ) as a platform to elucidate the implications of halogenation that can be extrapolated to living systems of much higher complexity. We show how single halogenations can fine-tune protein structures and dynamics of FtsZ with subtle perturbations collectively amplified by the process of FtsZ self-organization. Based on experiments and theories, we have gained valuable insights into the mechanism of halogen influence. The bending of FtsZ structures occurs by affecting surface charges and internal domain distances and is reflected in the decline of GTPase activities by reducing GTP binding energy during polymerization. Our results point to a better understanding of the physiological and pathological effects of protein halogenation and may contribute to the development of potential diagnostic tools.
Published in: Nature Communications, 10.1038/s41467-022-32535-2, Springer Nature