xCDxCDx‐PHD, a distinct type of PHD‐finger

P lant h omeo d omain (PHD) scaffolds are conserved protein modules in eukaryotes that typically recognize unstructured histone tails, and thus, play a critical role in chromatin signaling. Being a zinc‐finger, the sequences of PHD‐fingers, since their origin, have diverged. However, certain sequence signature features in PHD‐finger sequences suggest that there could be different subtypes among PHD‐fingers. One such subtype is the PHD‐finger featuring the xCDxCDx motif in the treble clef. Even though PHD‐finger binding‐site is rich in negatively charged residues for interacting with positively charged histone proteins, we note that a number of nonpolar amino acids are enriched at the binding site of xCDxCDx‐PHD subtype. These nonpolar residues have likely coevolved with the xCDxCDx motif. In general, coevolving residues contribute to: ( a ) folding of a scaffold, and/or ( b ) function (e.g., substrate binding). Here, we probed the coevolving residues of xCDxCDx‐PHD to find which of the two contributions ( a or b or both) do they make. We have learned that the coevolving residue of xCDxCDx‐PHD are necessary for peptide binding and contribute little toward folding of xCDxCDx‐PHD scaffold. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .