9B8D

Structure of Legionella pneumophila Ceg10

9B8D の概要

• エントリーDOI: 10.2210/pdb9b8d/pdb
• 分子名称: Ceg10, 1,2-ETHANEDIOL, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: bacterial, effector, pathogen, hydrolase
• 由来する生物種: Legionella pneumophila
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27151.60

構造登録者

Tomchick, D.R.,Heisler, D.B.,Alto, N.M. (登録日: 2024-03-29, 公開日: 2024-04-10, 最終更新日: 2024-05-29)

主引用文献

Embry, A.,Baggett, N.S.,Heisler, D.B.,White, A.,de Jong, M.F.,Kocsis, B.L.,Tomchick, D.R.,Alto, N.M.,Gammon, D.B.
Exploiting bacterial effector proteins to uncover evolutionarily conserved antiviral host machinery.
Plos Pathog., 20:e1012010-e1012010, 2024

PubMed Abstract: Arboviruses are a diverse group of insect-transmitted pathogens that pose global public health challenges. Identifying evolutionarily conserved host factors that combat arbovirus replication in disparate eukaryotic hosts is important as they may tip the balance between productive and abortive viral replication, and thus determine virus host range. Here, we exploit naturally abortive arbovirus infections that we identified in lepidopteran cells and use bacterial effector proteins to uncover host factors restricting arbovirus replication. Bacterial effectors are proteins secreted by pathogenic bacteria into eukaryotic hosts cells that can inhibit antimicrobial defenses. Since bacteria and viruses can encounter common host defenses, we hypothesized that some bacterial effectors may inhibit host factors that restrict arbovirus replication in lepidopteran cells. Thus, we used bacterial effectors as molecular tools to identify host factors that restrict four distinct arboviruses in lepidopteran cells. By screening 210 effectors encoded by seven different bacterial pathogens, we identify several effectors that individually rescue the replication of all four arboviruses. We show that these effectors encode diverse enzymatic activities that are required to break arbovirus restriction. We further characterize Shigella flexneri-encoded IpaH4 as an E3 ubiquitin ligase that directly ubiquitinates two evolutionarily conserved proteins, SHOC2 and PSMC1, promoting their degradation in insect and human cells. We show that depletion of either SHOC2 or PSMC1 in insect or human cells promotes arbovirus replication, indicating that these are ancient virus restriction factors conserved across invertebrate and vertebrate hosts. Collectively, our study reveals a novel pathogen-guided approach to identify conserved antimicrobial machinery, new effector functions, and conserved roles for SHOC2 and PSMC1 in virus restriction.

PubMed: 38753575
DOI: 10.1371/journal.ppat.1012010

実験手法

X-RAY DIFFRACTION (1.72 Å)