Temporal control of IDR multimerization
and phase separation in
vitro. (A) Schematic representation for chemogenic dimerization of
RGG polypeptides to form mesoscale liquid-like protein condensates.
(B) Representative images of liquid droplet formation through increased
domain valency upon addition of dimerizer, Rap. Recombinant RGG-FKBP
and RGG-FRB proteins, in the absence of Rap, do not form condensates
in a buffer containing 10 μM protein and 0.2 μM tracer
(RGG-GFP-RGG). Scale bar, 10 μm. Addition of Rap to the reaction
rapidly induces dimerization, causing condensate formation similar
to the RGG-RGG constitutive dimer. (C and D) Quantitation of the kinetics
of droplet formation upon equimolar addition of Rap. Average of three
independent trials. Shaded area, StDev. (E) Kinetics of solution clouding
after addition of dimerizer in spectrophotometric turbidity assays;
average of three experiments area shown. (F) Phase transition temperature
measured by turbidity assay shows induced dimerization of RGG-FKBP
and RGG-FRB with Rap shifts the cloud point to higher temperatures,
similar to constitutive RGG-RGG dimer; average of three experiments.
(G) Representative images from photobleaching and recovery of condensates
composed of Rap-mediated RGG-FKBP/RGG-FRB dimers marked by 0.2 μM
RGG-GFP-RGG tracer. Scale bar 5 μm. (H) Quantification of FRAP
indicating similar recovery kinetics of Rap-induced vs constitutive
RGG-RGG dimers. n = 30 condensates from two independent
trials.