Events

Evolutionary changes in the host-virus interactome can alter the course of infection, but which and how often interactions evolve and how this is realized at the interface residue level, remain largely unexplored. Here, we focus on viral mimicry of motifs and domains of host proteins, that allow efficient binding to host proteins by mimicking interfaces of host proteins. Our results show that in contrast to the prevailing view of rapid interface evolution between host- and viral-interacting proteins, viruses evolved to target highly conserved host proteins. The similarity between viral mimics and their host mimicked proteins limits host capacity to escape interaction with mimics, enabling efficient viral interaction with host targets through mimicry. These results have important implications for our understanding of zoonotic events where novel host-virus protein interactions may evolve and for designing new antiviral drugs targeting interface regions between host and viral proteins.

Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. Monoubiquitinated histone H2B-K120 is a hallmark of actively transcribed genes that plays multiple roles in activating transcription, while monoubiquitinated histone H2A-K119 is abundant in heterochromatin, which is transcriptionally silent. Our structural studies have revealed how histone H2B is specifically ubiquitinated and deubiquitinated, and ubiquitinated H2B stimulates histone methylation. We have also shown how ubiquitin can regulate access to the nucleosome acidic patch, a hotspot for interactions with other chromatin-modifying enzymes. I will also discuss recent studies of a histone kinase that has an unusual mode of binding nucleosomes.