Structural basis for arginine glycosylation of host substrates by bacterial effector proteins

Park, Jun Bae, Kim, Young Hun, Yoo, Youngki, Kim, Juyeon, Jun, Sung-Hoon, Cho, Jin Won, El-Qaidi, Samir, Walpole, Samuel, Monaco, Serena, Garcia-Garcia, Ana A., Wu, Miaomiao, Hays, Michael P., Hurtado-Guerrero, Ramon, Angulo, Jesus, Hardwidge, Philip R., Shin, Jeon-Soo and Cho, Hyun-Soo (2018) Structural basis for arginine glycosylation of host substrates by bacterial effector proteins. Nature Communications, 9. ISSN 2041-1723

[img]
Preview
PDF (Published manuscript) - Published Version
Available under License Creative Commons Attribution.

Download (2316kB) | Preview

    Abstract

    The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Pharmacy
    Depositing User: LivePure Connector
    Date Deposited: 17 Oct 2018 15:32
    Last Modified: 09 Apr 2019 13:49
    URI: https://ueaeprints.uea.ac.uk/id/eprint/68586
    DOI: 10.1038/s41467-018-06680-6

    Actions (login required)

    View Item