Crystal structure and functional analysis of the histone methyltransferase SET7/9.

Cell ·Vol. 111 ·No. 1 ·2002-10-04 ·Pages 105-15

Wilson JR, Jing C, Walker PA, Martin SR, Howell SA, Blackburn GM, Gamblin SJ, Xiao B

Abstract

Methylation of lysine residues in the N-terminal tails of histones is thought to represent an important component of the mechanism that regulates chromatin structure. The evolutionarily conserved SET domain occurs in most proteins known to possess histone lysine methyltransferase activity. We present here the crystal structure of a large fragment of human SET7/9 that contains a N-terminal beta-sheet domain as well as the conserved SET domain. Mutagenesis identifies two residues in the C terminus of the protein that appear essential for catalytic activity toward lysine-4 of histone H3. Furthermore, we show how the cofactor AdoMet binds to this domain and present biochemical data supporting the role of invariant residues in catalysis, binding of AdoMet, and interactions with the peptide substrate.

MeSH Terms

Amino Acid Sequence Binding Sites Catalysis Catalytic Domain Circular Dichroism Crystallography, X-Ray DNA Methylation DNA Mutational Analysis DNA-Binding Proteins/chemistry Drosophila Proteins/chemistry Escherichia coli/metabolism Histone Methyltransferases Histone-Lysine N-Methyltransferase Histones/metabolism Humans Lysine/chemistry Methyltransferases Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/chemistry Peptides/chemistry Polycomb Repressive Complex 2 Protein Binding Protein Conformation Protein Methyltransferases Protein Structure, Secondary Protein Structure, Tertiary Repressor Proteins/chemistry Sequence Homology, Amino Acid Substrate Specificity Transcription Factors Urea/pharmacology

Chemicals

DNA-Binding Proteins Drosophila Proteins Histones Nuclear Proteins Peptides Repressor Proteins Transcription Factors Trl protein, Drosophila Urea Histone Methyltransferases Methyltransferases Protein Methyltransferases E(z) protein, Drosophila Histone-Lysine N-Methyltransferase Polycomb Repressive Complex 2 SETD7 protein, human Lysine

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Wilson Jonathan R

Structural Biology Group, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.

Jing Chun

Walker Philip A

Martin Stephen R

Howell Steven A

Blackburn G Michael

Gamblin Steven J

Xiao Bing

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(02)00964-9

Published

2002-10-04

Pages

105-15

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(02)00964-9 View journal details

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Crystal structure and functional analysis of the histone methyltransferase SET7/9.

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