Structural and functional characterization of legionella pneumophila effector mavl

Kevin Voth, Shivani Pasricha, Ivy Yeuk Wah Chung, Rachelia R. Wibawa, Engku Nuraishah Huda E. Zainudin, Elizabeth L. Hartland, Miroslaw Cygler

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Legionella pneumophila is a Gram-negative intracellular pathogen that causes Legionnaires' disease in elderly or immunocompromised individuals. This bacterium relies on the Dot/Icm (De-fective in organelle trafficking/Intracellular multiplication) Type IV Secretion System (T4SS) and a large (>330) set of effector proteins to colonize the host cell. The structural variability of these effec-tors allows them to disrupt many host processes. Herein, we report the crystal structure of MavL to 2.65 Å resolution. MavL adopts an ADP-ribosyltransferase (ART) fold and contains the distinctive ligand-binding cleft of ART proteins. Indeed, MavL binds ADP-ribose with Kd of 13 µM. Structural overlay of MavL with poly-(ADP-ribose) glycohydrolases (PARGs) revealed a pair of aspartate residues in MavL that align with the catalytic glutamates in PARGs. MavL also aligns with ADP-ribose “reader” proteins (proteins that recognize ADP-ribose). Since no glycohydrolase activity was ob-served when incubated in the presence of ADP-ribosylated PARP1, MavL may play a role as a signaling protein that binds ADP-ribose. An interaction between MavL and the mammalian ubiquitin-conjugating enzyme UBE2Q1 was revealed by yeast two-hybrid and co-immunoprecipitation ex-periments. This work provides structural and molecular insights to guide biochemical studies aimed at elucidating the function of MavL. Our findings support the notion that ubiquitination and ADP-ribosylation are global modifications exploited by L. pneumophila.

Original languageEnglish
Article number1802
Number of pages18
JournalBiomolecules
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2021

Keywords

  • ADP-ribosyltransferase fold
  • Cellular localization
  • Crystal structure
  • Legionella effector
  • Protein-protein interactions

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