Sequence grammar underlying the unfolding and phase separation of globular proteins.

ABSTRACT: Aberrant phase separation of globular proteins is associated with many diseases. Here, we use a model protein system to understand how the unfolded states of globular proteins drive phase separation and the formation of unfolded protein deposits (UPODs). We find that for UPODs to form, the concentrations of unfolded molecules must be above a threshold value. Additionally, unfolded molecules must possess appropriate sequence grammars to drive phase separation. While UPODs recruit molecular chaperones, their compositional profiles are also influenced by synergistic physicochemical interactions governed by the sequence grammars of unfolded proteins and cellular proteins. Overall, the driving forces for phase separation and the compositional profiles of UPODs are governed by the sequence gramm

SUBMITTER: Ruff KM 

PROVIDER: S-EPMC10846692 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature