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Condensation of the N-terminal domain of human topoisomerase 1 is driven by electrostatic interactions and tuned by its charge distribution

Int J Biol Macromol. 2023-10; 
Greta Bianchi, Marco Mangiagalli, Diletta Ami, Junaid Ahmed, Silvia Lombardi, Sonia Longhi, Antonino Natalello, Peter Tompa, Stefania Brocca
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摘要

Liquid-liquid phase separation (LLPS) is pivotal in forming biomolecular condensates, which are crucial in several biological processes. Intrinsically disordered regions (IDRs) are typically responsible for driving LLPS due to their multivalency and high content of charged residues that enable the establishment of electrostatic interactions. In our study, we examined the role of charge distribution in the condensation of the disordered N-terminal domain of human topoisomerase I (hNTD). hNTD is densely charged with oppositely charged residues evenly distributed along the sequence. Its LLPS behavior was compared with that of charge permutants exhibiting varying degrees of charge segregation. At low salt concentra... More

關鍵詞

Biomolecular condensates, Charge decoration, Charge patterning, Human topoisomerase 1, Intrinsically disordered proteins
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