Format

Send to

Choose Destination
Nat Commun. 2018 Oct 16;9(1):4283. doi: 10.1038/s41467-018-06680-6.

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

Author information

1
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
2
Department of Microbiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
3
Center for Electron Microscopy Research, Korea Basic Science Institute, Ochang, Chungbuk, 28119, Republic of Korea.
4
College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
5
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
6
BIFI, University of Zaragoza, BIFI-IQFR (CSIC) Joint Unit, Mariano Esquillor s/n, Campus Rio Ebro, Edificio I+D, Zaragoza, 50018, Spain.
7
BIFI, University of Zaragoza, BIFI-IQFR (CSIC) Joint Unit, Mariano Esquillor s/n, Campus Rio Ebro, Edificio I+D, Zaragoza, 50018, Spain. rhurtado@bifi.es.
8
Fundación ARAID, 50018, Zaragoza, Spain. rhurtado@bifi.es.
9
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. j.angulo@uea.ac.uk.
10
Department of Microbiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. jsshin6203@yuhs.ac.
11
Severance Biomedical Science Institute and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. jsshin6203@yuhs.ac.
12
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. hscho8@yonsei.ac.kr.

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.

PMID:
30327479
PMCID:
PMC6191443
DOI:
10.1038/s41467-018-06680-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center