Structure and Histone Binding Properties of the Vps75-Rtt109 Chaperone-Lysine Acetyltransferase Complex

Dan Su,Qi Hu,Hui Zhou,James R Thompson,Rui-Ming Xu,Zhiguo Zhang,Georges Mer

doi:10.1074/jbc.c111.220715

Abstract

The histone chaperone Vps75 presents the remarkable property of stimulating the Rtt109-dependent acetylation of several histone H3 lysine residues within (H3-H4)(2) tetramers. To investigate this activation mechanism, we determined x-ray structures of full-length Vps75 in complex with full-length Rtt109 in two crystal forms. Both structures show similar asymmetric assemblies of a Vps75 dimer bound to an Rtt109 monomer. In the Vps75-Rtt109 complexes, the catalytic site of Rtt109 is confined to an enclosed space that can accommodate the N-terminal tail of histone H3 in (H3-H4)(2). Investigation of Vps75-Rtt109-(H3-H4)(2) and Vps75-(H3-H4)(2) complexes by NMR spectroscopy-probed hydrogen/deuterium exchange suggests that Vps75 guides histone H3 in the catalytic enclosure. These findings clarify the basis for the enhanced acetylation of histone H3 tail residues by Vps75-Rtt109.

Highlights

The acetylation of histones at several lysine residues contributes to the regulated disassembly and assembly of nucleosomes, a process essential for DNA replication and repair, and gene transcription
The lysine acetyltransferase Rtt109 has been implicated in the acetylation of Lys-9, Lys-14, Lys-23, Lys-27, and Lys-56 in newly synthesized histone H3, modifications that are associated with nucleosome assembly during DNA replication and transcription [1,2,3,4,5,6]
Asf1 is essential for the acetylation of Lys-56 within the globular core of H3-H4 in vivo, whereas Vps75 is dispensable for this enzymatic reaction

Summary

Introduction

The acetylation of histones at several lysine residues contributes to the regulated disassembly and assembly of nucleosomes, a process essential for DNA replication and repair, and gene transcription. To investigate this activation mechanism, we determined x-ray structures of full-length Vps75 in complex with full-length Rtt109 in two crystal forms. In the Vps75-Rtt109 complexes, the catalytic site of Rtt109 is confined to an enclosed space that can accommodate the N-terminal tail of histone H3 in (H3-H4)2.

Results

Conclusion