Abstract
WD repeat protein-5 (WDR5), a well-established protein hub, plays an important role in multiple cellular pathways. It is crucial to the regulation of methylation of histone H3 Lys 4 (H3K4) by the SET1 family of proteins. There are 6 known SET1 proteins: MLL1, MLL2, MLL3, MLL4, SETd1A and SETd1B. The WDR5 interacting (Win) motif of these proteins mediates their interactions with WDR5. This motif has a highly conserved Arg residue that inserts into the Win-site cavity. While the binding affinities of SET1 family members with WDR5 have been explored before, the kinetics of these interactions have not been quantified.
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