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Title: Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7

Abstract

We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate "tailless nucleosomes", which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity. Here, we report structural and biochemical studies on JMJD5/7 to understand the basis of substrate recognition and catalysis mechanism by this JmjC subfamily. Recognition between these enzymes and histone substrates is specific, which is reflected by the binding data between enzymes and substrates. High structural similarity between JMJD5 and JMJD7 is reflected by the shared common substrates and high binding affinity. However, JMJD5 does not bind to arginine methylated histone tails with additional lysine acetylation while JMJD7 does not bind to arginine methylated histone tails with additional lysine methylation. Furthermore, the complex structures of JMJD5 and arginine derivatives revealed a Tudor domain-like binding pocket to accommodate the methylated sidechain of arginine, but not lysine. There also exists a glutamine close to the catalytic center, which may suggest a unique imidic acid mediated catalytic mechanism for proteolysis by JMJD5/7.

Authors:
 [1];  [2];  [2];  [2];  [2];  [3]; ORCiD logo [3];  [4];  [5];  [2];  [1]; ORCiD logo [2];  [1];  [2]
  1. National Jewish Health, Denver, CO (United States); Univ. of Colorado, Denver, CO (United States); Howard Hughes Medical Institute, Denver, CO (United States)
  2. National Jewish Health, Denver, CO (United States); Univ. of Colorado, Denver, CO (United States)
  3. Chinese Agricultural Univ., Beijing (China)
  4. Univ. of Science and Technology of China, Hefei (China)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1560549
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

Citation Formats

Liu, Haolin, Wang, Chao, Lee, Schuyler, Ning, Fangkun, Wang, Yang, Zhang, Qianqian, Chen, Zhongzhou, Zang, Jianye, Nix, Jay, Dai, Shaodong, Marrack, Philippa, Hagman, James, Kappler, John, and Zhang, Gongyi. Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7. United States: N. p., 2018. Web. doi:10.1038/s41598-018-21432-8.
Liu, Haolin, Wang, Chao, Lee, Schuyler, Ning, Fangkun, Wang, Yang, Zhang, Qianqian, Chen, Zhongzhou, Zang, Jianye, Nix, Jay, Dai, Shaodong, Marrack, Philippa, Hagman, James, Kappler, John, & Zhang, Gongyi. Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7. United States. doi:10.1038/s41598-018-21432-8.
Liu, Haolin, Wang, Chao, Lee, Schuyler, Ning, Fangkun, Wang, Yang, Zhang, Qianqian, Chen, Zhongzhou, Zang, Jianye, Nix, Jay, Dai, Shaodong, Marrack, Philippa, Hagman, James, Kappler, John, and Zhang, Gongyi. Mon . "Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7". United States. doi:10.1038/s41598-018-21432-8. https://www.osti.gov/servlets/purl/1560549.
@article{osti_1560549,
title = {Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7},
author = {Liu, Haolin and Wang, Chao and Lee, Schuyler and Ning, Fangkun and Wang, Yang and Zhang, Qianqian and Chen, Zhongzhou and Zang, Jianye and Nix, Jay and Dai, Shaodong and Marrack, Philippa and Hagman, James and Kappler, John and Zhang, Gongyi},
abstractNote = {We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate "tailless nucleosomes", which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity. Here, we report structural and biochemical studies on JMJD5/7 to understand the basis of substrate recognition and catalysis mechanism by this JmjC subfamily. Recognition between these enzymes and histone substrates is specific, which is reflected by the binding data between enzymes and substrates. High structural similarity between JMJD5 and JMJD7 is reflected by the shared common substrates and high binding affinity. However, JMJD5 does not bind to arginine methylated histone tails with additional lysine acetylation while JMJD7 does not bind to arginine methylated histone tails with additional lysine methylation. Furthermore, the complex structures of JMJD5 and arginine derivatives revealed a Tudor domain-like binding pocket to accommodate the methylated sidechain of arginine, but not lysine. There also exists a glutamine close to the catalytic center, which may suggest a unique imidic acid mediated catalytic mechanism for proteolysis by JMJD5/7.},
doi = {10.1038/s41598-018-21432-8},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {2018},
month = {2}
}

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Works referenced in this record:

Integration, scaling, space-group assignment and post-refinement
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144
  • DOI: 10.1107/S0907444909047374