김성옥 (School of Medicine, Tufts University (현 세종대학교))

한빛사논문

조회166

School of Medicine, Tufts University (현 세종대학교)

CV File 248 kb

Nat. Commun., Aug 30 2024, 15 (1) 7479 | https://doi.org/10.1038/s41467-024-51272-2 Sde proteins coordinate ubiquitin utilization and phosphoribosylation to establish and maintain the Legionella replication vacuole

Kristin M. Kotewicz^1,6, Mengyun Zhang ^1,4,6, Seongok Kim ^1,5,6, Meghan S. Martin ², Atish Roy Chowdhury ¹, Albert Tai ³, Rebecca A. Scheck ²& Ralph R. Isberg^1,*

¹Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
²Department of Chemistry, Tufts University, Medford, MA, USA.
³Department of Immunology, Tufts University School of Medicine, Boston, MA, USA.
⁴Present address: Global Health Drug Discovery Institute, Haidian Beijing, China.
⁵Present address: Department of Food Science & Biotechnology, Carbohydrate Bioproduct Research Center, College of Life Science, Sejong University, Seoul, South Korea.
⁶These authors contributed equally: Kristin M. Kotewicz, Mengyun Zhang, Seongok Kim.

^*Corresponding author: correspondence to Ralph R. Isberg

Abstract

The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification of Reticulon 4 (Rtn4). Sde proteins have two additional activities of unclear relevance to the infection process: K63 linkage-specific deubiquitination and phosphoribosyl modification of polyubiquitin (pR-Ub). We show here that the deubiquitination activity (DUB) stimulates ER rearrangements while pR-Ub protects the replication vacuole from cytosolic surveillance by autophagy. Loss of DUB activity is tightly linked to lowered pR-Ub modification of Rtn4, consistent with the DUB activity fueling the production of pR-Ub-Rtn4. In parallel, phosphoribosyl modification of polyUb, in a region of the protein known as the isoleucine patch, prevents binding by the autophagy adapter p62. An inability of Sde mutants to modify polyUb results in immediate p62 association, a critical precursor to autophagic attack. The ability of Sde WT to block p62 association decays quickly after bacterial infection, as predicted by the presence of previously characterized L. pneumophila effectors that inactivate Sde and remove polyUb. In sum, these results show that the accessory Sde activities act to stimulate ER rearrangements and protect from host innate immune sensing in a temporal fashion.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-09-02)
연구진국외 연구진
분야 생명과학 > 미생물학

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