Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor

ABSTRACT: Human cytomegalovirus (CMV) is a ubiquitously distributed pathogen whose rodent counterparts such as mouse and rat CMV serve as common infection models. Here, we conducted global proteome profiling of rat CMV-infected cells and uncovered a pronounced loss of the transcription factor STAT2, which is crucial for antiviral interferon signalling. Via deletion mutagenesis, we found that the viral protein E27 is required for CMV-induced STAT2 depletion. Cellular and in vitro analyses showed that E27 exploits host-cell Cullin4-RING ubiquitin ligase (CRL4) complexes to induce poly-ubiquitylation and proteasomal degradation of STAT2. Cryo-electron microscopy revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors called DCAFs (DDB1- and Cullin4-associated factors),

SUBMITTER: Dr. Vu Thuy Khanh Le-Trilling 

PROVIDER: S-SCDT-10_15252-EMBJ_2022112351 | biostudies-other |

REPOSITORIES: biostudies-other