Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase

Xing Zhang; Hisashi Tamaru; Seema I. Khan; John R. Horton; Lisa J. Keefe; Eric U. Selker; Xiaodong Cheng

doi:10.1016/S0092-8674(02)00999-6

Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase

Xing Zhang, Hisashi Tamaru, Seema I. Khan, John R. Horton, Lisa J. Keefe, Eric U. Selker, Xiaodong Cheng

Research output: Contribution to journal › Article › peer-review

221 Scopus citations

Abstract

AdoMet-dependent methylation of histones is part of the "histone code" that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 Å resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn₃Cys₉ zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.

Original language	English (US)
Pages (from-to)	117-127
Number of pages	11
Journal	Cell
Volume	111
Issue number	1
DOIs	https://doi.org/10.1016/S0092-8674(02)00999-6
State	Published - Oct 4 2002
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase",

abstract = "AdoMet-dependent methylation of histones is part of the {"}histone code{"} that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 {\AA} resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn3Cys9 zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.",

author = "Xing Zhang and Hisashi Tamaru and Khan, {Seema I.} and Horton, {John R.} and Keefe, {Lisa J.} and Selker, {Eric U.} and Xiaodong Cheng",

note = "Funding Information: We thank Dr. V. Ramakrishnan (Cambridge) for recombinant histone, Ms. Fang Fang Yin for making 3C-S mutant, and Drs. D. Reines, P.W. Wade, and R.M. Blumenthal for critical comments on the manuscript. These studies were supported in part by U.S. Public Health Services grants GM49245 and GM61355 (to X.Z. and X.C.) and GM35690 (to E.U.S). X-ray data were collected at beamline 17-ID in the facilities of IMCA-CAT at the Advanced Photon Source. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract number W-31-109-Eng-38. ",

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AU - Zhang, Xing

AU - Tamaru, Hisashi

AU - Khan, Seema I.

AU - Horton, John R.

AU - Keefe, Lisa J.

AU - Selker, Eric U.

AU - Cheng, Xiaodong

N1 - Funding Information: We thank Dr. V. Ramakrishnan (Cambridge) for recombinant histone, Ms. Fang Fang Yin for making 3C-S mutant, and Drs. D. Reines, P.W. Wade, and R.M. Blumenthal for critical comments on the manuscript. These studies were supported in part by U.S. Public Health Services grants GM49245 and GM61355 (to X.Z. and X.C.) and GM35690 (to E.U.S). X-ray data were collected at beamline 17-ID in the facilities of IMCA-CAT at the Advanced Photon Source. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract number W-31-109-Eng-38.

PY - 2002/10/4

Y1 - 2002/10/4

N2 - AdoMet-dependent methylation of histones is part of the "histone code" that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 Å resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn3Cys9 zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.

AB - AdoMet-dependent methylation of histones is part of the "histone code" that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 Å resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn3Cys9 zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.

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Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase

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