Structural basis for the binding selectivity of human CDY chromodomains [article]

Cheng Dong, Yanli Liu, Tianjie Lyu, Serap Beldar, Kelsey Lamb, Wolfram Tempel, Yanjun Li, Zoey Li, Lindsey James, Su Qin, Yun Wang, Jinrong Min
2019 bioRxiv   pre-print
The CDY (Chromodomain on the Y) family is a small family of chromodomain containing proteins, whose chromodomains closely resemble those in HP1 and Polycomb. The CDY proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and
more » ... e proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. Based on our structural, binding and mutagenesis data, we synthesized a more CDYL1/2 selective peptidic ligand UNC4850. Our work provides critical implications that CDYL1b's role in the regulation of neural development is dependent on its recognition of lysine-methylated ARKS motifs.
doi:10.1101/820647 fatcat:up5vlzmmwnbtbih2ig6dxtub3m