Cytomegalovirus immediate-early 1 proteins form a structurally distinct protein class with adaptations determining cross-species barriers
Schweininger J, Scherer M, Rothemund F, Schilling EM, Worz S, Stamminger T, Muller Y (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 17
Journal Issue: 8
DOI: 10.1371/journal.ppat.1009863
Abstract
Author summary Cytomegaloviruses have evolved in very close association with their hosts resulting in a highly species-specific replication. Cell-intrinsic proteins, known as restriction factors, constitute important barriers for cross-species infection of viruses. All cytomegaloviruses characterized so far express an abundant immediate-early protein, termed IE1, that binds to the cellular restriction factor promyelocytic leukemia protein (PML) and antagonizes its repressive activity on viral gene expression. Here, we present the crystal structures of the PML-binding domains of rat and human cytomegalovirus IE1. Despite low amino-acid sequence identity both proteins share a highly similar and unique fold forming a distinct protein class. Functional characterization revealed a common mechanism of PML antagonization. However, we also detected that the respective IE1 proteins only interact with PML proteins of the natural host species. Interestingly, expression of HCMV IE1 allows rat cytomegalovirus infection in human cells. This indicates that the cellular restriction factor PML forms an important barrier for cross-species infection of cytomegaloviruses that might be overcome by adaptation of IE1 protein function. Our data suggest that the cytomegalovirus IE1 structure represents an evolutionary optimized protein fold targeting PML proteins via coiled-coil interactions.
Authors with CRIS profile
Johannes Schweininger
Lehrstuhl für Biotechnik (Proteinstruktur und -design)
Yves Muller
Lehrstuhl für Biotechnik (Proteinstruktur und -design)
Involved external institutions
Germany (DE)How to cite
APA:
Schweininger, J., Scherer, M., Rothemund, F., Schilling, E.-M., Worz, S., Stamminger, T., & Muller, Y. (2021). Cytomegalovirus immediate-early 1 proteins form a structurally distinct protein class with adaptations determining cross-species barriers. PLoS Pathogens, 17(8). https://doi.org/10.1371/journal.ppat.1009863
MLA:
Schweininger, Johannes, et al. "Cytomegalovirus immediate-early 1 proteins form a structurally distinct protein class with adaptations determining cross-species barriers." PLoS Pathogens 17.8 (2021).
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