Altered dynamics may drift pathological fibrillization in membraneless organelles

B. Tüű-Szabó, G. Hoffka, N. Duro, M. Fuxreiter

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Protein phase transition can generate non-membrane bound cellular compartments, which can convert from liquid-like to solid-like states. While the molecular driving forces of phase separation have been largely understood, much less is known about the mechanisms of material-state conversion. We apply a recently developed algorithm to describe the weak interaction network of multivalent motifs, and simulate the effect of pathological mutations. We demonstrate that linker dynamics is critical to the material-state of biomolecular condensates. We show that linker flexibility/mobility is a major regulator of the weak, heterogeneous meshwork of multivalent motifs, which promotes phase transition and maintains a liquid-like state. Decreasing linker dynamics increases the propensity of amyloid-like fragments via hampering the motif-exchange and reorganization of the weak interaction network. In contrast, increasing linker mobility may compensate rigidifying mutations, suggesting that the meshwork of weak, variable interactions may provide a rescue mechanism from aggregation. Motif affinity, on the other hand, has a moderate impact on fibrillization. Here we demonstrate that the fuzzy framework provides an efficient approach to handle the intricate organization of membraneless organelles, and could also be applicable to screen for pathological effects of mutations.

Original languageEnglish
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Organelles
Phase transitions
Phase Transition
Mutation
Liquids
Amyloid
Phase separation
Agglomeration
Proteins

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Altered dynamics may drift pathological fibrillization in membraneless organelles. / Tüű-Szabó, B.; Hoffka, G.; Duro, N.; Fuxreiter, M.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, 01.01.2019.

Research output: Contribution to journalArticle

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