Crystal Structure of Cytomegalovirus IE1 Protein Reveals Targeting of TRIM Family Member PML via Coiled-Coil Interactions

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Research of the last few years has revealed that microbial infections are not only controlled by innate and adaptive immune mechanisms, but also by cellular restriction factors, which give cells the capacity to resist pathogens. PML nuclear bodies (PML-NBs) are dot-like nuclear structures representing multiprotein complexes that consist of the PML protein, a member of the TRIM family of proteins, as well as a multitude of additional regulatory factors. PML-NB components act as a barrier against many viral infections; however, viral antagonistic proteins have evolved to modify PML-NBs, thus abrogating this cellular defense. Here, we delineate the molecular basis for antagonization by the immediate-early protein IE1 of the herpesvirus human cytomegalovirus. We present the first crystal structure for the evolutionary conserved core domain (IE1CORE) of primate cytomegalovirus IE1, which exhibits a novel, unusual fold. IE1CORE modifies PML-NBs by releasing other PML-NB proteins into the nucleoplasm which is sufficient to antagonize intrinsic immunity. Importantly, IE1CORE shares secondary structure features with the coiled-coil domain (CC) of TRIM factors, and we demonstrate strong binding of IE1 to the PML-CC. We propose that IE1CORE sequesters PML and possibly other TRIM family members via an extended binding surface formed by the coiled-coil domain.

Vyšlo v časopise: Crystal Structure of Cytomegalovirus IE1 Protein Reveals Targeting of TRIM Family Member PML via Coiled-Coil Interactions. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004512
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004512

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