Fungal Rtt109 Histone Acetyltransferase is an Unexpected Structural Homolog of Metazoan P300/CBP

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2008 Jun 24

PMID 18568037

Citations 78

Authors

Yong Tang

Marc A Holbert

Hugo Wurtele

Katrina Meeth

Walter Rocha

Marlene Gharib

Eva Jiang

Pierre Thibault

Alain Verreault

Alain Verrault

Philip A Cole

Ronen Marmorstein

Affiliations

Soon will be listed here.

Abstract

Rtt109, also known as KAT11, is a recently characterized fungal-specific histone acetyltransferase (HAT) that modifies histone H3 lysine 56 (H3K56) to promote genome stability. Rtt109 does not show sequence conservation with other known HATs and depends on association with either of two histone chaperones, Asf1 or Vps75, for HAT activity. Here we report the X-ray crystal structure of an Rtt109-acetyl coenzyme A complex and carry out structure-based mutagenesis, combined with in vitro biochemical studies of the Rtt109-Vps75 complex and studies of Rtt109 function in vivo. The Rtt109 structure reveals noteworthy homology to the metazoan p300/CBP HAT domain but exhibits functional divergence, including atypical catalytic properties and mode of cofactor regulation. The structure reveals a buried autoacetylated lysine residue that we show is also acetylated in the Rtt109 protein purified from yeast cells. Implications for understanding histone substrate and chaperone binding by Rtt109 are discussed.

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