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Connecting Coil-to-Globule Transitions to Full Phase Diagrams for Intrinsically Disordered Proteins.


ABSTRACT: Phase separation is thought to underlie spatial and temporal organization that is required for controlling biochemical reactions in cells. Multivalence of interaction motifs, also known as stickers, is a defining feature of proteins that drive phase separation. Intrinsically disordered proteins with stickers uniformly distributed along the linear sequence can serve as scaffold molecules that drive phase separation. The sequence-intrinsic contributions of disordered proteins to phase separation can be discerned by computing or measuring sequence-specific phase diagrams. These help to delineate the combinations of protein concentration and a suitable control parameter, such as temperature, that support phase separation. Here, we present an approach that combines detailed simulations with a numerical adaptation of an analytical Gaussian cluster theory to enable the calculation of sequence-specific phase diagrams. Our approach leverages the known equivalence between the driving forces for single-chain collapse in dilute solutions and the driving forces for phase separation in concentrated solutions. We demonstrate the application of the theory-aided computations through calculation of phase diagrams for a set of archetypal intrinsically disordered low-complexity domains. We also leverage theories to compute sequence-specific percolation lines and thereby provide a thermodynamic framework for hardening transitions that have been observed for many biomolecular condensates.

SUBMITTER: Zeng X 

PROVIDER: S-EPMC7376131 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Connecting Coil-to-Globule Transitions to Full Phase Diagrams for Intrinsically Disordered Proteins.

Zeng Xiangze X   Holehouse Alex S AS   Chilkoti Ashutosh A   Mittag Tanja T   Pappu Rohit V RV  

Biophysical journal 20200623 2


Phase separation is thought to underlie spatial and temporal organization that is required for controlling biochemical reactions in cells. Multivalence of interaction motifs, also known as stickers, is a defining feature of proteins that drive phase separation. Intrinsically disordered proteins with stickers uniformly distributed along the linear sequence can serve as scaffold molecules that drive phase separation. The sequence-intrinsic contributions of disordered proteins to phase separation c  ...[more]

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