Phase Separation and Single-Chain Compactness of Charged Disordered Proteins Are Strongly Correlated.

Liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is a major undergirding factor in the regulated formation of membraneless organelles in the cell. The phase behavior of an IDP is sensitive to its amino acid sequence. Here we apply a recent random-phase-approximation polymer theory to investigate how the tendency for multiple chains of a protein to phase-separate, as characterized by the critical temperature T∗cr, is related to the protein's single-chain average radius of gyration 〈Rg〉. For a set of sequences containing different permutations of an equal number of positively and negatively charged residues, we found a striking correlation T∗cr ∼ 〈Rg〉-γ with γ as large as ∼6.0, indicating that electrostatic effects have similarly significant impact on promoting single-chain conformational compactness and phase separation. Moreover, T∗cr ∝ -SCD, where SCD is a recently proposed "sequence charge decoration" parameter determined solely by sequence information. Ramifications of our findings for deciphering the sequence dependence of IDP phase separation are discussed.

• Publication year

  2017

• Venue

  Biophysical Journal

• Publication date

  2017-03-08

• Fields of study

  Biology, Materials Science, Physics, Chemistry, Medicine

• Identifiers
  DOI 10.1016/j.bpj.2017.04.021arXiv 1703.02725PMID 28483149PMCID PMC5448239
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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