Host FIH-Mediated Asparaginyl Hydroxylation of Translocated Legionella pneumophila Effectors

Frontiers in Cellular and Infection Microbiology

Alam, Nawsad¹  Merchant, Michael²  Best, Ashley³  Price, Christopher³  Von Dwingelo, Juanita³  Lawrenz, Matthew B.³  Jones, Snake³  Schueler-Furman, Ora⁴  Kwaik, Yousef A.⁴ 

[1] Center for Predictive Medicine, College of Medicine, University of Louisville, Louisville, KY, USA;Department of Medicine-Renal, College of Medicine, University of Louisville, Louisville, KY, USA;Department of Microbiology and Immunology, College of Medicine, University of Louisville, Louisville, KY, USA;Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel

关键词: FIH;    asparagine hydroxylation;    ankyrin;    Dot/Icm;    AnkB;    Hypoxia-inducible factor (HIF);    Bacterial Pathogenesis;    Legionella;   

DOI  :  10.3389/fcimb.2017.00054

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

FIH-mediated post-translational modification through asparaginyl hydroxylation of eukaryotic proteins impacts regulation of protein-protein interaction. We have identified the FIH recognition motif in eleven Legionella pneumophila translocated effectors, YopM of Yersinia, IpaH4.5 of Shigella and an ankyrin protein of Rickettsia. Mass spectrometry analyses of the AnkB and AnkH effectors of L. pneumophila confirm their asparaginyl hydroxylation. Consistent with localization of the AnkB effector to the Legionella-containing vacuole (LCV) membrane and its modification by FIH, our data show that FIH and its two interacting proteins, Mint3 and MT1-MMP are acquired by the LCV in a Dot/Icm type IV secretion-dependent manner. Chemical inhibition or RNAi-mediated knockdown of FIH promotes LCV-lysosomes fusion, diminishes decoration of the LCV with polyubiquitinated proteins, and abolishes intra-vacuolar replication of L. pneumophila. These data show acquisition of the host FIH by a pathogen-containing vacuole and that asparaginyl-hydroxylation of translocated effectors is indispensable for their function.

【 授权许可】

CC BY