Structural Basis for the Binding Selectivity of Human CDY Chromodomains
Cheng Dong1, Yanli Liu2, Tian-Jie Lyu3
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Cell Chemical Biology
|May 30, 2020
Summary
Chromodomain on the Y (CDY) proteins are crucial for sperm production and brain function. This study reveals the structural basis for CDY protein binding specificity to methylated histone motifs, impacting neurological development and fertility.
Area of Science:
- Molecular Biology
- Epigenetics
- Structural Biology
Background:
- Chromodomain on the Y (CDY) proteins are vital for spermatogenesis and brain development.
- Dysregulation of CDY proteins is linked to male infertility and neurological disorders.
- CDY chromodomains recognize lysine-methylated ARKS motifs in histone and non-histone proteins.
Purpose of the Study:
- Elucidate the structural basis for CDY1 and CDYL2 selective binding to methylated histone marks.
- Investigate the molecular mechanisms of CDYL2 binding specificity.
- Explore the role of lysine-methylated ARKS motif recognition in CDYL1b's neural development function.
Main Methods:
- X-ray crystallography to determine protein structures.
- Biochemical assays to assess binding preferences.
- Pharmacological studies using a selective CDYL1/2 compound (UNC4850).
Main Results:
- Structural basis for CDY1 binding to H3K9me3.
- Structural basis for CDYL2 preferential binding to H3tK27me3 over H3K27me3.
- UNC4850 provided insights into CDYL2 binding mechanisms.
Conclusions:
- CDY protein binding specificity is context-dependent.
- Understanding CDY binding mechanisms has implications for male infertility and neurological diseases.
- CDYL1b's function in neural development relies on recognizing methylated ARKS motifs.
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