Phase separation is an important mechanism that mediates the compartmentalization of proteins in cells.Proteins that can undergo phase separation in cells share certain typical sequence features,like intrinsically dis...Phase separation is an important mechanism that mediates the compartmentalization of proteins in cells.Proteins that can undergo phase separation in cells share certain typical sequence features,like intrinsically disordered regions(IDRs)and multiple modular domains.Sequencebased analysis tools are commonly used in the screening of these proteins.However,current phase separation predictors are mostly designed for IDR-containing proteins,thus inevitably overlook the phase-separating proteins with relatively low IDR content.Features other than amino acid sequence could provide crucial information for identifying possible phase-separating proteins:protein–protein interaction(PPI)networks show multivalent interactions that underlie phase separation process;post-translational modifications(PTMs)are crucial in the regulation of phase separation behavior;spherical structures revealed in immunofluorescence(IF)images indicate condensed droplets formed by phase-separating proteins,distinguishing these proteins from non-phaseseparating proteins.Here,we summarize the sequence-based tools for predicting phaseseparating proteins and highlight the importance of incorporating PPIs,PTMs,and IF images into phase separation prediction in future studies.展开更多
基金supported by the National Key R&D Program of China(Grant No.2018YFA0507504)the National Natural Science Foundation of China(Grant Nos.61773025 and 32070666)
文摘Phase separation is an important mechanism that mediates the compartmentalization of proteins in cells.Proteins that can undergo phase separation in cells share certain typical sequence features,like intrinsically disordered regions(IDRs)and multiple modular domains.Sequencebased analysis tools are commonly used in the screening of these proteins.However,current phase separation predictors are mostly designed for IDR-containing proteins,thus inevitably overlook the phase-separating proteins with relatively low IDR content.Features other than amino acid sequence could provide crucial information for identifying possible phase-separating proteins:protein–protein interaction(PPI)networks show multivalent interactions that underlie phase separation process;post-translational modifications(PTMs)are crucial in the regulation of phase separation behavior;spherical structures revealed in immunofluorescence(IF)images indicate condensed droplets formed by phase-separating proteins,distinguishing these proteins from non-phaseseparating proteins.Here,we summarize the sequence-based tools for predicting phaseseparating proteins and highlight the importance of incorporating PPIs,PTMs,and IF images into phase separation prediction in future studies.
