Phase separation and single-chain compactness of charged disordered proteins are strongly correlated

Abstract

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 $T_{\mathrm{cr}}^{\ast }$, is related to the protein's single-chain average radius of gyration $⟨R_{\mathrm{g}}⟩$. For a set of sequences containing different permutations of an equal number of positively and negatively charged residues, we found a striking correlation $T_{\mathrm{cr}}^{\ast }\sim ⟨R_{\mathrm{g}}{⟩}^{-\gamma }$ with $\gamma$ as large as $\sim 6.0$, indicating that electrostatic effects have similarly significant impact on promoting single-chain conformational compactness and phase separation. Moreover, $T_{\mathrm{cr}}^{\ast }\propto -\mathrm{SCD}$, 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.

4 page, 3 figures, accepted for publication in Biophysical Journal as a Letter

References in corpus (2)

• Sequence-specific polyampholyte phase separation in membraneless organelles
• Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins

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