Multivalent arrays of short linear motifs (SLiMs) and their associated binding domains (BDs) have been found to form condensates.
Currently, the available modules mostly make use of natural SLiM-BD interaction pairs, but future work could involve developing bio-orthogonal modules.
SLiM-BD modules have been used both in vitro and in cells.
+ common molecular grammar
+ compatible with endogenous MLO clients
+ properties tunable via spacers
- potential interference with endogenous MLOs (if endogenous binding domains are used)
>SUMO (Banani et al., 2016)
>SIM (Banani et al., 2016)
>SH3 (Li et al., 2012)
>PRM (Li et al., 2012)
How to tune SLiM-BD arrays according to the sticker-spacer framework?
There are three ways on how to tune the phase diagram and/or material properties of IDR-based condensates.
1. Number of stickers: Simply increasing or decreasing the number of stickers in each array has been shown respectively decrease/increase the IDR saturation concentration (Li et al., 2012; Banani et al., 2016).
2. Sticker strength: Altering the affinity of SLiM-BD modules will alter lifetime of crosslinks and drive changes in material properties.
3: Spacer properties: The length and flexibility of the spacers may affect condensation and gelation properties (Harmon et al., 2017).