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SLiM-BD

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.

PROS:
+ common molecular grammar
+ compatible with endogenous MLO clients
+ properties tunable via spacers

CONS:
- potential interference with endogenous MLOs (if endogenous binding domains are used)

SUMO-SIM sequences:

>SUMO (Banani et al., 2016)
MSEEKPKEGVKTENDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQQQTVV

>SIM (Banani et al., 2016)
KVDVIDLTIESSSDEEEDPPAKR

SUMO-SIM sequences:

>SH3 (Li et al., 2012)
GHMDLNMPAYVKFNYMAEREDELSLIKGTKVIVMEKSSDGWWRGSYNGQVGWFPSNYVTEEGDSPL

>PRM (Li et al., 2012)
CGGSWGGSKKKKTAPTPPKRS

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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).