Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling
The demethylase activity of KDM5A is allosterically enhanced by binding of histone H3 to its PHD1 reader domain, through an unknown mechanism. Here the authors show that the PHD1 domain drives ligand-induced allosteric stimulation by stabilizing the binding of substrate to the catalytic domain.
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2019-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-018-07829-z |
| _version_ | 1818342103144464384 |
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| author | James E. Longbotham Cynthia M. Chio Venkatasubramanian Dharmarajan Michael J. Trnka Idelisse Ortiz Torres Devrishi Goswami Karen Ruiz Alma L. Burlingame Patrick R. Griffin Danica Galonić Fujimori |
| author_facet | James E. Longbotham Cynthia M. Chio Venkatasubramanian Dharmarajan Michael J. Trnka Idelisse Ortiz Torres Devrishi Goswami Karen Ruiz Alma L. Burlingame Patrick R. Griffin Danica Galonić Fujimori |
| author_sort | James E. Longbotham |
| collection | DOAJ |
| description | The demethylase activity of KDM5A is allosterically enhanced by binding of histone H3 to its PHD1 reader domain, through an unknown mechanism. Here the authors show that the PHD1 domain drives ligand-induced allosteric stimulation by stabilizing the binding of substrate to the catalytic domain. |
| first_indexed | 2024-12-13T16:09:22Z |
| format | Article |
| id | doaj.art-8af366d414d64557aaf7cda67d5a31e7 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-12-13T16:09:22Z |
| publishDate | 2019-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-8af366d414d64557aaf7cda67d5a31e72022-12-21T23:38:59ZengNature PortfolioNature Communications2041-17232019-01-0110111210.1038/s41467-018-07829-zHistone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodelingJames E. Longbotham0Cynthia M. Chio1Venkatasubramanian Dharmarajan2Michael J. Trnka3Idelisse Ortiz Torres4Devrishi Goswami5Karen Ruiz6Alma L. Burlingame7Patrick R. Griffin8Danica Galonić Fujimori9Department of Cellular and Molecular Pharmacology, University of CaliforniaDepartment of Cellular and Molecular Pharmacology, University of CaliforniaDepartment of Molecular Medicine, The Scripps Research InstituteDepartment of Pharmaceutical Chemistry, University of CaliforniaChemistry and Chemical Biology Graduate Program, University of CaliforniaDepartment of Molecular Medicine, The Scripps Research InstituteTETRAD Graduate Program, University of CaliforniaDepartment of Pharmaceutical Chemistry, University of CaliforniaDepartment of Molecular Medicine, The Scripps Research InstituteDepartment of Cellular and Molecular Pharmacology, University of CaliforniaThe demethylase activity of KDM5A is allosterically enhanced by binding of histone H3 to its PHD1 reader domain, through an unknown mechanism. Here the authors show that the PHD1 domain drives ligand-induced allosteric stimulation by stabilizing the binding of substrate to the catalytic domain.https://doi.org/10.1038/s41467-018-07829-z |
| spellingShingle | James E. Longbotham Cynthia M. Chio Venkatasubramanian Dharmarajan Michael J. Trnka Idelisse Ortiz Torres Devrishi Goswami Karen Ruiz Alma L. Burlingame Patrick R. Griffin Danica Galonić Fujimori Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling Nature Communications |
| title | Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling |
| title_full | Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling |
| title_fullStr | Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling |
| title_full_unstemmed | Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling |
| title_short | Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling |
| title_sort | histone h3 binding to the phd1 domain of histone demethylase kdm5a enables active site remodeling |
| url | https://doi.org/10.1038/s41467-018-07829-z |
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