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Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides

  • Gabryelczyk, Bartosz Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore - Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, Finland
  • Cai, Hao Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore -
  • Shi, Xiangyan School of Physical and Mathematical Sciences, NTU, 21 Nanyang Link, Singapore -
  • Sun, Yue Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore
  • Swinkels, Piet J.M. Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore - Physical Chemistry and Soft Matter, Wageningen University, Netherlands
  • Salentinig, Stefan Laboratory for Biointerfaces, Department Materials Meet Life, EMPA, St-Gallen, Switzerland - Department of Chemistry, University of Fribourg, Switzerland
  • Pervushin, Konstantin School of Biological Sciences, NTU, Singapore
  • Miserez, Ali Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore - School of Biological Sciences, NTU, Singapore
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    29.11.2019
Published in:
  • Nature Communications. - 2019, vol. 10, no. 1, p. 1–12
English Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) is involved in both intracellular membraneless organelles and extracellular tissues. Despite growing understanding of LLPS, molecular-level mechanisms behind this process are still not fully established. Here, we use histidine-rich squid beak proteins (HBPs) as model IDPs to shed light on molecular interactions governing LLPS. We show that LLPS of HBPs is mediated though specific modular repeats. The morphology of separated phases (liquid-like versus hydrogels) correlates with the repeats’ hydrophobicity. Solution-state NMR indicates that LLPS is a multistep process initiated by deprotonation of histidine residues, followed by transient hydrogen bonding with tyrosine, and eventually by hydrophobic interactions. The microdroplets are stabilized by aromatic clustering of tyrosine residues exhibiting restricted molecular mobility in the nano-to-microsecond timescale according to solid- state NMR experiments. Our findings provide guidelines to rationally design pH- responsive peptides with LLPS ability for various applications, including bioinspired protocells and smart drug-delivery systems.
Faculty
Faculté des sciences et de médecine
Department
Département de Chimie
Language
  • English
Classification
Chemistry
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https://folia.unifr.ch/unifr/documents/308265
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