Structural Basis for the Binding Selectivity of Human CDY Chromodomains

Dong，Cheng1; Liu，Yanli2,3; Lyu，Tian Jie4; Beldar，Serap5; Lamb，Kelsey N.6; Tempel，Wolfram5; Li，Yanjun5; Li，Zoey4; James，Lindsey I.6; Qin，Su5,7; Wang，Yun4,8; Min，Jinrong3,5,9

2020

10.1016/j.chembiol.2020.05.007

Cell Chemical Biology   影响因子和分区

2451-9456

2451-9448

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.

CDY chromodomain histone H3 neural development small-molecule inhibitor

SCI

英语

通讯

Genome Canada through Ontario Genomics Institute[OGI-055] ; Innovative Medicines Initiative (EU/EFPIA) (ULTRA-DD)[115766] ; US Department of Energy Office of Biological and Environmental Research[DE-AC02-06CH11357] ; NSERC[RGPIN-2016-06300] ; National Natural Science Foundation of China[31500615][31500613][31530028][31720103908][81821092][31900865] ; Central China Normal University (CCNU) from the college's basic research and operation of Ministry of Education (MOE)[CCNU18TS020]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000551596000009

CELL PRESS

2-s2.0-85086375189

Scopus

1.Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin,300070,China
2.College of Pharmaceutical Sciences,Soochow University,Suzhou,199 Ren'ai Road,215123,China
3.Hubei Key Laboratory of Genetic Regulation and Integrative Biology,School of Life Sciences,Central China Normal University,Wuhan,430079,China
4.Neuroscience Research Institute and Department of Neurobiology,School of Basic Medical Sciences,Key Laboratory for Neuroscience,Ministry of Education/National Health Commission,Peking University,Beijing,100191,China
5.Structural Genomics Consortium,University of Toronto,Toronto,101 College Street,M5G 1L7,Canada
6.Center for Integrative Chemical Biology and Drug Discovery,Division of Chemical Biology and Medicinal Chemistry,UNC Eshelman School of Pharmacy,University of North Carolina at Chapel Hill,Chapel Hill,27599,United States
7.Life Science Research Center,Southern University of Science and Technology,Shenzhen,518055,China
8.PKU-IDG/McGovern Institute for Brain Research,Peking University,Beijing,100871,China
9.Department of Physiology,University of Toronto,Toronto,M5S 1A8,Canada

Dong，Cheng,Liu，Yanli,Lyu，Tian Jie,et al. Structural Basis for the Binding Selectivity of Human CDY Chromodomains[J]. Cell Chemical Biology,2020,27(7):827-+.

Dong，Cheng.,Liu，Yanli.,Lyu，Tian Jie.,Beldar，Serap.,Lamb，Kelsey N..,...&Min，Jinrong.(2020).Structural Basis for the Binding Selectivity of Human CDY Chromodomains.Cell Chemical Biology,27(7),827-+.

Dong，Cheng,et al."Structural Basis for the Binding Selectivity of Human CDY Chromodomains".Cell Chemical Biology 27.7(2020):827-+.