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Here we explore how binding specificity is conveyed in PDZ (postsynaptic density protein-95/discs large/zonula occludens-1) domains, small interaction modules that recognize various proteins by binding to an extended C terminus.
To facilitate a quantitative interpretation of array data, for instance for factors (antibodies and protein modules) that recognize more than one epitope, we utilized heatmap representations (Fig. 2b), which have been widely used for the presentation of nucleotide array data.
This allowed the fusion of two or three such molecules to generate a five-finger protein that recognizes a 15 bp site on the top strand and the fusion of two to three different modules that recognize a 15 bp site on the bottom strand that lies 5 6 bp away.
The CxxC zinc finger domains are modules that recognize unmethylated cytosine residues in a CpG dinucleotide context.
Currently, OPEN reagents include modules that recognize all 16 possible GNN triplets (i.e., DNA triplets beginning with G, followed by any nucleotide in the second and third positions), as well as several TNN triplets.
TALENs use DNA-recognition modules that recognize single base pairs, linked to the same FokI-derived cleavage domain that is used in ZFNs (Gaj et al. 2013; Joung and Sander 2013).
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BRDs are protein interaction modules that recognizing ε-N-acetyl-lysine (εAc-Lys) motifs found in histone tails and are promising protein protein interaction (PPI) targets.
The Src homology 2 (SH2) domain is the most prevalent protein binding module that recognizes phosphotyrosine.
The ADD domain functions as a reader module that recognizes histone H3 "K4methylationmethylation pattern and tolerates additional H3S10 phosphorylation to facilitate heterochromatin targeting of ATRX (Iwase et al., 2011; Noh et al., 2015).
They comprise a donor-acceptor pair (typically CFP and YFP) flanking a module that contains a phosphorylation sequence directed towards the relevant kinase, and a phosphopeptide-binding module that recognizes the phosphorylated sequence.
Our study describes the first systematic screening effort to identify small molecules that bind to a PHD finger namely the PHD finger from human Pygo, a chromatin reader module that recognizes the histone H3K4me mark associated with active transcription.
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