Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies

AbstractMultivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network of multiple proteins and RNAs, and their competing molecular interactions play key roles in regulating the condensate composition and structure. Employing a ternary system comprising of a prion-like polypeptide (PLP), arginine-rich polypeptide (RRP), and RNA, we show that competition between the PLP and RNA for a single shared partner, the RRP, leads to RNA-induced demixing of PLP-RRP condensates into stable coexisting phases—homotypic PLP condensates and heterotypic RRP-RNA condensates. The morphology of these biphasic condensates (non-engulfing/ partial engulfing/ complete engulfing) is determined by the RNA-to-RRP stoichiometry and the hierarchy of intermolecular interactions, providing a glimpse of the broad range of multiphasic patterns that are accessible to these condensates. Our findings provide a minimal set of physical rules that govern the composition and spatial organization of multicomponent and multiphasic biomolecular condensates.

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Sequence-encoded and Composition-dependent Protein-RNA Interactions Control Multiphasic Condensate Morphologies

10.1101/2020.08.30.273748 ◽

2020 ◽

Cited By ~ 3

Author(s):

Taranpreet Kaur ◽

Muralikrishna Raju ◽

Ibraheem Alshareedah ◽

Richoo B. Davis ◽

Davit A. Potoyan ◽

...

Keyword(s):

Phase Separation ◽

Ternary System ◽

Intermolecular Interactions ◽

Molecular Interactions ◽

Spatial Organization ◽

Dense Network ◽

Minimal Set ◽

Composition And Structure ◽

Coexisting Phases ◽

Dependent Protein

ABSTRACTMultivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network of multiple proteins and RNAs, and their competing molecular interactions play key roles in regulating the condensate composition and structure. Employing a ternary system comprising of a prion-like polypeptide (PLP), arginine-rich polypeptide (RRP), and RNA, we show that competition between the PLP and RNA for a single shared partner, the RRP, leads to RNA-induced demixing of PLP-RRP condensates into stable coexisting phases−homotypic PLP condensates and heterotypic RRP-RNA condensates. The morphology of these biphasic condensates (non-engulfing/ partial engulfing/ complete engulfing) is determined by the RNA-to-RRP stoichiometry and the hierarchy of intermolecular interactions, providing a glimpse of the broad range of multiphasic patterns that are accessible to these condensates. Our findings provide a minimal set of physical rules that govern the composition and spatial organization of multicomponent and multiphasic biomolecular condensates.

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Structure formation in the process of phase separation of ternary system of “poly-D,L-lactide – tetraglycol – antisolvent”

Physics and Chemistry of Materials Treatment ◽

10.30791/0015-3214-2018-4-71-80 ◽

2018 ◽

pp. 71-80

Author(s):

A.V. Mironov ◽

◽

A.O. Mariyanats ◽

O.A. Mironova ◽

V.K. Popov ◽

...

Keyword(s):

Phase Separation ◽

Ternary System ◽

Structure Formation

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Molecular interactions between lecithin and sphingomyelin. Temperature- and composition-dependent phase separation.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)40183-9 ◽

1977 ◽

Vol 252 (13) ◽

pp. 4449-4457 ◽

Cited By ~ 6

Author(s):

S H Untrach ◽

G G Shipley

Keyword(s):

Phase Separation ◽

Molecular Interactions

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Prediction of vapour-liquid equilibrium: Theory, computer techniques and application to permanent gas mixtures at pressures in excess of 5 bar

Australian Journal of Chemistry ◽

10.1071/ch9772583 ◽

1977 ◽

Vol 30 (12) ◽

pp. 2583 ◽

Cited By ~ 3

Author(s):

CP Hicks ◽

CL Young

Keyword(s):

Phase Separation ◽

Fluid Model ◽

Gas Mixtures ◽

Liquid Equilibrium ◽

Equal Area ◽

Closed Equation ◽

Coexisting Phases ◽

Temperature And Pressure ◽

Two Parameter ◽

Theory And Experiment

A technique for calculating the composition of two coexisting phases in equilibrium at a given temperature and pressure is described. The method is applicable, in principle, to any one-fluid model and any two- parameter closed equation of state. The philosophy of the technique is similar to that used in previous work on critical points.�� Values of (∂G/∂x2)T,P are calculated for mole fraction compositions ranging from zero to unity in small steps in order to locate (∂G/∂x2)T,P loops. Around each loop there is a region of phase separation and the compositions of coexisting phases are found by the usual equal-area line technique. �� The use of the method is briefly illustrated by comparison with the experimental results for simple gas mixtures. The agreement between theory and experiment is satisfactory.

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Molecular interactions shaping the tetraspanin web

Biochemical Society Transactions ◽

10.1042/bst20160284 ◽

2017 ◽

Vol 45 (3) ◽

pp. 741-750 ◽

Cited By ~ 47

Author(s):

Sjoerd J. van Deventer ◽

Vera-Marie E. Dunlock ◽

Annemiek B. van Spriel

Keyword(s):

Molecular Interactions ◽

Intracellular Signaling ◽

Spatial Organization ◽

Complex Mixture ◽

Point Of View ◽

Intramolecular Interactions ◽

Fundamental Understanding ◽

High Degree ◽

Partner Proteins ◽

Insight Into

To facilitate the myriad of different (signaling) processes that take place at the plasma membrane, cells depend on a high degree of membrane protein organization. Important mediators of this organization are tetraspanin proteins. Tetraspanins interact laterally among themselves and with partner proteins to control the spatial organization of membrane proteins in large networks called the tetraspanin web. The molecular interactions underlying the formation of the tetraspanin web were hitherto mainly described based on their resistance to different detergents, a classification which does not necessarily correlate with functionality in the living cell. To look at these interactions from a more physiological point of view, this review discusses tetraspanin interactions based on their function in the tetraspanin web: (1) intramolecular interactions supporting tetraspanin structure, (2) tetraspanin–tetraspanin interactions supporting web formation, (3) tetraspanin–partner interactions adding functional partners to the web and (4) cytosolic tetraspanin interactions regulating intracellular signaling. The recent publication of the first full-length tetraspanin crystal structure sheds new light on both the intra- and intermolecular tetraspanin interactions that shape the tetraspanin web. Furthermore, recent molecular dynamic modeling studies indicate that the binding strength between tetraspanins and between tetraspanins and their partners is the complex sum of both promiscuous and specific interactions. A deeper insight into this complex mixture of interactions is essential to our fundamental understanding of the tetraspanin web and its dynamics which constitute a basic building block of the cell surface.

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