6V2H

Crystal structure of CDYL2 in complex with H3tK27me3

Summary for 6V2H

• Entry DOI: 10.2210/pdb6v2h/pdb
• Related: 6V2D
• Descriptor: Chromodomain Y-like protein 2, H3tK27me3, NICKEL (II) ION, ... (4 entities in total)
• Functional Keywords: histone, chromodomain, structural genomics, structural genomics consortium, sgc, gene regulation
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 52677.35

Authors

Dong, C.,Tempel, W.,Walker, J.R.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2019-11-22, release date: 2019-12-25, Last modification date: 2023-10-11)

Primary citation

Dong, C.,Liu, Y.,Lyu, T.J.,Beldar, S.,Lamb, K.N.,Tempel, W.,Li, Y.,Li, Z.,James, L.I.,Qin, S.,Wang, Y.,Min, J.
Structural Basis for the Binding Selectivity of Human CDY Chromodomains.
Cell Chem Biol, 27:827-838.e7, 2020

PubMed Abstract: The CDY (chromodomain on the Y) 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 non-histone 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. In addition, we use a CDYL1/2-selective compound, UNC4850, to gain further insight into the molecular mechanisms underlying CDYL2 binding specificity. Our work also provides critical implications that CDYL1b's role in the regulation of neural development is dependent on its recognition of the lysine-methylated ARKS motif.

PubMed: 32470319
DOI: 10.1016/j.chembiol.2020.05.007

Experimental method

X-RAY DIFFRACTION (2.6 Å)