A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif

Sorgeloos, Frederic; Peeters, Michael; Hayashi, Yohei; Borghese, Fabian; Capelli, Nicolas; Drappier, Melissa; Cesaro, Teresa; Colau, Didier; Stroobant, Vincent; Vertommen, Didier; de Bodt, Gregory; Messe, Stephane; Forne, Ignasi; Mueller-Planitz, Felix; Collet, Jean-Francois und Michiels, Thomas (2022): A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 119, Nr. 5, e2114647119

Abstract

Microbes have been coevolving with their host for millions of years, exploiting host resources to their own benefit. We show that viral and bacterial pathogens convergently evolved to hijack cellular mitogen-activated protein kinase (MAPK) p90-ribosomal S6-kinases (RSKs). Theiler's virus leader (L) protein binds RSKs and prevents their dephosphorylation, thus maintaining the kinases active. Recruitment of RSKs enables L-protein-mediated inhibition of eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2 or PKR) and stress granule formation. Strikingly, ORF45 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) and YopM protein of Yersinia use the same peptide motif as L to recruit and activate RSKs. All three proteins interact with a conserved surface-located loop of RSKs, likely acting as an allosteric regulation site. Some unrelated viruses and bacteria thus evolved to harness RSKs in a common fashion, yet to target distinct aspects of innate immunity. As documented for Varicella zoster virus ORF11, additional pathogens likely evolved to hijack RSKs, using a similar short linear motif.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0027-8424
• Sprache: Englisch