A recent formulation of random-phase-approximation polymer theory for disordered protein phase separation is applied to investigate how the tendency for multiple chains of a protein to phase separate, as characterized by the critical temperature T^*_{\rm cr}, is related to the protein's single-chain average radius of gyration \langle R _g \rangle. For a set of thirty model sequences containing different permutations of an equal number of positively and negatively charged residues, we found a striking correlation T^*_{\rm cr}\sim \langle R _g \rangle^{- \nu } with \nu\approx 3.5-6.0 , indicating that electrostatic effects have similar impact in promoting single-chain conformational compactness and phase separation. We found further that T^*_{\rm cr}\propto -{\rm SCD}, where SCD is a recently proposed "sequence charge decoration" parameter that is determined solely by sequence information. Ramification of our findings for deciphering the sequence dependence of the phase separation of intrinsically disordered proteins are discussed.
Liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is a major undergirding factor in the regulated formation of URLanelles 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^*_{\rm cr}, is related to the protein's single-chain average radius of gyration \langle R _{\rm g \rangle. For a set of sequences containing different permutations of an equal number of positively and negatively charged residues, we found a striking correlation T^*_{\rm cr}\sim \langle R _{\rm g \rangle^{- \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^*_{\rm cr}\propto -{\rm 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.
R
A recent formulation of
Liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is a major undergirding factor in the regulated formation of URLanelles in the cell. The phase behavior of an IDP is sensitive to its amino acid sequence. Here we apply a recent
R
polymer theory for disordered protein phase separation is applied to
polymer theory to
R
_g
_{\rm g
D
thirty model
R
_g
_{\rm g
R
\nu
\gamma
R
\nu\approx 3.5-6.0
\gamma as large as \sim 6.0
R
similar impact in
similarly significant impact on
R
We found further that
Moreover,
D
that is
R
Ramification
Ramifications
R
the phase separation of intrinsically disordered proteins
IDP phase separation