Voth, Kevin and Pasricha, Shivani and Yeuk, Ivy Wah Chung and Wibawa, Rachelia R. and E. Zainudin, Engku Nuraishah Huda and Hartland, Elizabeth L. and Cygler, Miroslaw (2021) Structural and functional characterization of Legionella pneumophila effector MavL. Biomolecules, 11 (12). ISSN 2218-273X
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Abstract
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 (Defective 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 effectors 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 observed 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 ubiquitinconjugating enzyme UBE2Q1 was revealed by yeast two-hybrid and co-immunoprecipitation experiments. 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.
| Item Type: | Article (Journal) |
|---|---|
| Uncontrolled Keywords: | Legionella effector; crystal structure; ADP-ribosyltransferase fold; protein-protein interactions; cellular localization |
| Subjects: | Q Science > QR Microbiology R Medicine > RA Public aspects of medicine > RA643 Communicable Diseases and Public Health |
| Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): | Kulliyyah of Pharmacy > Department of Basic Medical Sciences |
| Depositing User: | Dr Engku Nuraishah Huda E.Zainudin |
| Date Deposited: | 02 Dec 2021 13:23 |
| Last Modified: | 02 Dec 2021 13:23 |
| URI: | http://irep.iium.edu.my/id/eprint/94249 |
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