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Halogenation of tyrosine perturbs large-scale protein self-organization

Title: Halogenation of tyrosine perturbs large-scale protein self-organization
Authors: Sun, Huan; Jia, Haiyang; Kendall, Olivia; Dragelj, Jovan; Kubyshkin, Vladimir; Baumann, Tobias; Mroginski, Maria-Andrea; Schwille, Petra; Budisa, Nediljko
Publication Year: 2023
Collection: TU Berlin: Deposit Once
Subject Terms: 500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften; chemical modification; perturbations; synthetic biology
Description: 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. ; DFG, 252961272, GRK 2062: Molekulare Prinzipien der Synthetischen Biologie ; DFG, 390540038, EXC 2008: Unifying Systems in Catalysis "UniSysCat"
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
DOI: 10.14279/depositonce-17900
Availability: https://depositonce.tu-berlin.de/handle/11303/19103; https://doi.org/10.14279/depositonce-17900
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.27031EA7
Database: BASE