Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling

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

doi:10.1038/s41467-018-07829-z

Nature Communications (Jan 2019)

Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling

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

Affiliations

James E. Longbotham: Department of Cellular and Molecular Pharmacology, University of California
Cynthia M. Chio: Department of Cellular and Molecular Pharmacology, University of California
Venkatasubramanian Dharmarajan: Department of Molecular Medicine, The Scripps Research Institute
Michael J. Trnka: Department of Pharmaceutical Chemistry, University of California
Idelisse Ortiz Torres: Chemistry and Chemical Biology Graduate Program, University of California
Devrishi Goswami: Department of Molecular Medicine, The Scripps Research Institute
Karen Ruiz: TETRAD Graduate Program, University of California
Alma L. Burlingame: Department of Pharmaceutical Chemistry, University of California
Patrick R. Griffin: Department of Molecular Medicine, The Scripps Research Institute
Danica Galonić Fujimori: Department of Cellular and Molecular Pharmacology, University of California

DOI: https://doi.org/10.1038/s41467-018-07829-z
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 12

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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