Abstract
Human cytomegalovirus (hCMV) immediate early 1 (IE1) protein associates with condensed chromatin of the host cell during mitosis. We have determined the structure of the chromatin-tethering domain (CTD) of IE1 bound to the nucleosome core particle, and discovered that IE1-CTD specifically interacts with the H2A-H2B acidic patch and impairs the compaction of higher-order chromatin structure. Our results suggest that IE1 loosens up the folding of host chromatin during hCMV infections.
Highlights
In eukaryotes, nuclear DNA is highly packaged into chromatin by histones
The complex of nucleosome core particle (NCP) with an immediate early 1 (IE1)-chromatin-tethering domain (CTD) peptide (a.a. 476–491) was obtained by soaking the peptide into preformed NCP crystals, and a 2.8 Astructure was solved by molecular replacement
The structure shows one molecule of IE1-CTD bound to the NCP (Figure 1A; Figure 1—figure supplement 1)
Summary
Nuclear DNA is highly packaged into chromatin by histones. The nucleosome, the basic repeating unit of chromatin, typically assembles 146–147 bp of DNA wrapped around a histone octamer consisting of two copies each of H3, H4, H2A and H2B (Luger et al, 1997a). Biochemistry Biophysics and structural biology eLife digest Most of the DNA in a cell is tightly wrapped around groups of proteins called histones, which gives the impression of beads on a string. These bead-like structures are called nucleosomes, and interactions between histones in different nucleosomes can link one nucleosome to another, to package the DNA into a very condensed form. The experiments show that small differences in the ways viral proteins interact with condensed DNA can change their effects on DNA packaging These findings may help scientists to better understand how the binding of the cytomegalovirus protein to the nucleosomes might affect this virus’s ability to infect or cause illness in humans. We provide an analysis of the structural basis for the interaction between the CTD of IE1 (IE1-CTD) and the nucleosome core particle (NCP) and explore the impact of their binding on the higher-order structure of chromatin
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