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Cited by 34Legionella and Acanthamoeba researchUbiquitin and proteasome pathwaysAutophagy in Disease and Therapy

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Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms

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Fu, Jiaqi, Li, Siying, Guan, Hongxin, Li, Chuang, Zhao, Yan-Bo, Chen, Tao-Tao, Xian, Wei, Zhang, Zhengrui, Liu, Yao, Guan, Qingtian, Wang, Jingting, Lu, Qiuhua, Kang, Lina, Zheng, Si-Ru, Li, Jinyu, Cao, Shoujing, Das, Chittaranjan, Liu, Xiaoyun, Song, Lei, Ouyang, Songying, Luo, Zhao-Qing·2024·Nature Communications
DOI 10.1038/s41467-024-50311-2PMC PMC11251166

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Abstract

The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.

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Metadata

Authors
Fu, J., Li, S., Guan, H., Li, C., Zhao, Y.-B., Chen, T.-T., Xian, W., Zhang, Z., Liu, Y., Guan, Q., Wang, J., Lu, Q., Kang, L., Zheng, S.-R., Li, J., Cao, S., Das, C., Liu, X., Song, L., Ouyang, S., & Luo, Z.-Q.
Affiliations
  • First Hospital of Jilin University (CN)
  • Fujian Normal University (CN)
  • Purdue University West Lafayette (US)
  • Peking University (CN)
  • Fuzhou University (CN)
Corresponding author
  • Liu, Xiaoyun
  • Song, Lei
  • Ouyang, Songying
  • Luo, Zhao-Qing
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-07-15
Volume
15
Issue
1
Pages
5953-5953
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-50311-2
PMC
PMC11251166
OpenAlex
W4400645073
Cited by
34
References
2
Citations by year
2026: 13 · 2025: 12 · 2024: 9
FWCI
10.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Foundation for the National Institutes of Health (R01AI127465, R01GM126296)
  • National Natural Science Foundation of China (32171265, 31900879, 31900879 and 32171265, 82172287, 22174003, 32370185, 82225028, 82225028 and 82172287, 21974002, 32270185)
  • Jilin University
  • Fujian Normal University ((Z0210509))
  • National Institutes of Health
  • National Key Research and Development Program of China (2022YFA1304500, 2021YFC2301403)
  • First Hospital of Jilin University
  • National Institute of General Medical Sciences (R01GM126296)
  • National Institute of Allergy and Infectious Diseases (R01AI127465)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
Legionella pneumophila, ubiquitin homeostasis, ADP-ribosylation, bacterial effector proteins, host-pathogen interaction

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