Structural and functional study of Legionella pneumophila effector RavA

Legionella pneumophila is an intracellular pathogen that causes Legionnaire's disease in humans. This bacterium can be found in freshwater environments as a free‐living organism, but it is also an intracellular parasite of protozoa. Human infection occurs when inhaled aerosolized pathogen comes...

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Bibliographic Details
Published in:	Protein science Vol. 30; no. 5; pp. 940 - 955
Main Authors:	Chung, Ivy Y. W., Li, Lei, Tyurin, Oleg, Gagarinova, Alla, Wibawa, Raissa, Li, Pengfei, Hartland, Elizabeth L., Cygler, Miroslaw
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-05-2021 Wiley Subscription Services, Inc
Subjects:	Adenosine Triphosphatases - chemistry Adenosine Triphosphatases - genetics Adenosine Triphosphatases - metabolism Alveoli Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism Baits crystal structure domain structure effector RavA Freshwater environments Full‐Length Papers Golgi apparatus Golgi localization Golgi localization sequence HEK293 Cells Homology Humans Infections Intracellular Legionella Legionella pneumophila Legionella pneumophila - enzymology Legionella pneumophila - genetics Legionnaire's disease Legionnaires' disease bacterium Localization Low level Macrophages Membranes Mucosa Parasites Pathogens Phagocytes Phagocytosis Phagosomes Protein Conformation, alpha-Helical Protein Domains Proteins Protozoa rab GTP-Binding Proteins - chemistry rab GTP-Binding Proteins - genetics rab GTP-Binding Proteins - metabolism Residues Secretory vesicles Structural analysis Structure-function relationships Yeasts Golgi localization sequence crystal structure domain structure effector RavA Legionella pneumophila Golgi localization
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Summary:	Legionella pneumophila is an intracellular pathogen that causes Legionnaire's disease in humans. This bacterium can be found in freshwater environments as a free‐living organism, but it is also an intracellular parasite of protozoa. Human infection occurs when inhaled aerosolized pathogen comes into contact with the alveolar mucosa and replicates in alveolar macrophages. Legionella enters the host cell by phagocytosis and redirects the Legionella‐containing phagosomes from the phagocytic maturation pathway. These nascent phagosomes fuse with ER‐derived secretory vesicles and membranes forming the Legionella‐containing vacuole. Legionella subverts many host cellular processes by secreting over 300 effector proteins into the host cell via the Dot/Icm type IV secretion system. The cellular function for many Dot/Icm effectors is still unknown. Here, we present a structural and functional study of L. pneumophila effector RavA (Lpg0008). Structural analysis revealed that the RavA consists of four ~85 residue long α‐helical domains with similar folds, which show only a low level of structural similarity to other protein domains. The ~90 residues long C‐terminal segment is predicted to be natively unfolded. We show that during L. pneumophila infection of human cells, RavA localizes to the Golgi apparatus and to the plasma membrane. The same localization is observed when RavA is expressed in human cells. The localization signal resides within the C‐terminal sequence C409WTSFCGLF417. Yeast‐two‐hybrid screen using RavA as bait identified RAB11A as a potential binding partner. RavA is present in L. pneumophila strains but only distant homologs are found in other Legionella species, where the number of repeats varies. PDB Code(s): 6WO6;
Bibliography:	Funding information Canadian Institutes of Health Research, Grant/Award Number: MOP 48370; National Research Council Canada; Western Economic Diversification Canada; Government of Saskatchewan; University of Saskatchewan; Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Funding information Canadian Institutes of Health Research, Grant/Award Number: MOP 48370; National Research Council Canada; Western Economic Diversification Canada; Government of Saskatchewan; University of Saskatchewan; Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation
ISSN:	0961-8368 1469-896X
DOI:	10.1002/pro.4057