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Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome.

Fang Q, Chen P, Wang M, Fang J, Yang N, Li G, Xu RM - Elife (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

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.

No MeSH data available.


Related in: MedlinePlus

An omit electron density map of the bound IE1-CTD.A stereo view of the simulated annealing (Fo-Fc) omit map showing the presence of IE1-CTD. The map is contoured at 2.5 σ level. A stick model of IE1-CTD is superimposed.DOI:http://dx.doi.org/10.7554/eLife.11911.004
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fig1s1: An omit electron density map of the bound IE1-CTD.A stereo view of the simulated annealing (Fo-Fc) omit map showing the presence of IE1-CTD. The map is contoured at 2.5 σ level. A stick model of IE1-CTD is superimposed.DOI:http://dx.doi.org/10.7554/eLife.11911.004

Mentions: The complex of NCP with an IE1-CTD peptide (a.a. 476–491) was obtained by soaking the peptide into preformed NCP crystals, and a 2.8 Å structure was solved by molecular replacement. The structure shows one molecule of IE1-CTD bound to the NCP (Figure 1A; Figure 1—figure supplement 1). The presence of only one IE1-CTD peptide in the complex structure is due to the availability of only one side of the NCP surface in the preformed crystal lattice, as in the case of NCP in complex with the latency-associated antigen (LANA) of Kaposi’s sarcoma-associated herpes virus (KSHV) (Barbera et al., 2006). The IE1-CTD peptide adopts an extended, v-shaped conformation with a short α-helix at its C-terminus. In the complex structure, IE1-CTD is well positioned into the acidic patch of the nucleosome formed by H2A and H2B (Figure 1A and B). IE1-CTD contacts histone H2B at two distinct sites, the C-terminal portion of α1 and the N-terminal half of αC, through van der Waals interaction and intermolecular hydrogen bonds via its mainchain groups. Specifically, the amide and carbonyl groups of Thr480 make hydrogen bonds with the mainchain carbonyl and the sidechain amide groups of Gln44 of H2B (amino acid residue numbering following that in the reference of Luger et al., 1997a); the amide and carbonyl groups of Val484 bond the carboxylate group of Glu110 and the nitrogen atom of the imidazole ring of His106, respectively (Figure 1B). IE1-CTD contacts histone H2A via a number of sidechain contacts. His481 makes one hydrogen bond with Glu56 of H2A; Thr485 and Ser487 each makes one hydrogen bond with Glu64 of H2A; and Arg486 makes hydrogen bonds with Glu61 on α2, as well as with Asp90 and Glu92 located on αC of histone H2A. In addition, Met483 of IE1-CTD is placed in a hydrophobic pocket consisting of Leu23, and the aliphatic portion of Glu56 and Tyr57.10.7554/eLife.11911.003Figure 1.Structure of the IE1-CTD–NCP complex.


Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome.

Fang Q, Chen P, Wang M, Fang J, Yang N, Li G, Xu RM - Elife (2016)

An omit electron density map of the bound IE1-CTD.A stereo view of the simulated annealing (Fo-Fc) omit map showing the presence of IE1-CTD. The map is contoured at 2.5 σ level. A stick model of IE1-CTD is superimposed.DOI:http://dx.doi.org/10.7554/eLife.11911.004
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4764553&req=5

fig1s1: An omit electron density map of the bound IE1-CTD.A stereo view of the simulated annealing (Fo-Fc) omit map showing the presence of IE1-CTD. The map is contoured at 2.5 σ level. A stick model of IE1-CTD is superimposed.DOI:http://dx.doi.org/10.7554/eLife.11911.004
Mentions: The complex of NCP with an IE1-CTD peptide (a.a. 476–491) was obtained by soaking the peptide into preformed NCP crystals, and a 2.8 Å structure was solved by molecular replacement. The structure shows one molecule of IE1-CTD bound to the NCP (Figure 1A; Figure 1—figure supplement 1). The presence of only one IE1-CTD peptide in the complex structure is due to the availability of only one side of the NCP surface in the preformed crystal lattice, as in the case of NCP in complex with the latency-associated antigen (LANA) of Kaposi’s sarcoma-associated herpes virus (KSHV) (Barbera et al., 2006). The IE1-CTD peptide adopts an extended, v-shaped conformation with a short α-helix at its C-terminus. In the complex structure, IE1-CTD is well positioned into the acidic patch of the nucleosome formed by H2A and H2B (Figure 1A and B). IE1-CTD contacts histone H2B at two distinct sites, the C-terminal portion of α1 and the N-terminal half of αC, through van der Waals interaction and intermolecular hydrogen bonds via its mainchain groups. Specifically, the amide and carbonyl groups of Thr480 make hydrogen bonds with the mainchain carbonyl and the sidechain amide groups of Gln44 of H2B (amino acid residue numbering following that in the reference of Luger et al., 1997a); the amide and carbonyl groups of Val484 bond the carboxylate group of Glu110 and the nitrogen atom of the imidazole ring of His106, respectively (Figure 1B). IE1-CTD contacts histone H2A via a number of sidechain contacts. His481 makes one hydrogen bond with Glu56 of H2A; Thr485 and Ser487 each makes one hydrogen bond with Glu64 of H2A; and Arg486 makes hydrogen bonds with Glu61 on α2, as well as with Asp90 and Glu92 located on αC of histone H2A. In addition, Met483 of IE1-CTD is placed in a hydrophobic pocket consisting of Leu23, and the aliphatic portion of Glu56 and Tyr57.10.7554/eLife.11911.003Figure 1.Structure of the IE1-CTD–NCP complex.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

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.

No MeSH data available.


Related in: MedlinePlus