Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

The Legionella effector LtpM is a new type of phosphoinositide-activated glucosyltransferase.

Nadezhda Levanova | Corinna Mattheis | Danielle Carson | Ka-Ning To | Thomas Jank | Gad Frankel | Klaus Aktories | Gunnar Neels Schroeder
The Journal of biological chemistry | 2019

Legionella pneumophila causes Legionnaires' disease, a severe form of pneumonia. L. pneumophila translocates more than 300 effectors into host cells via its Dot/Icm (Defective in organelle trafficking/Intracellular multiplication) type IV secretion system to enable its replication in target cells. Here, we studied the effector LtpM, which is encoded in a recombination hot spot in L. pneumophila Paris. We show that a C-terminal phosphoinositol 3-phosphate (PI3P)-binding domain, also found in otherwise unrelated effectors, targets LtpM to the Legionella-containing vacuole and to early and late endosomes. LtpM expression in yeast caused cytotoxicity. Sequence comparison and structural homology modeling of the N-terminal domain of LtpM uncovered a remote similarity to the glycosyltransferase (GT) toxin PaTox from the bacterium Photorhabdus asymbiotica; however, instead of the canonical DxD motif of GT-A type glycosyltransferases, essential for enzyme activity and divalent cation coordination, we found that a DxN motif is present in LtpM. Using UDP-glucose as sugar donor, we show that purified LtpM nevertheless exhibits glucohydrolase and autoglucosylation activity in vitro and demonstrate that PI3P binding activates LtpM's glucosyltransferase activity toward protein substrates. Substitution of the aspartate or the asparagine in the DxN motif abolished the activity of LtpM. Moreover, whereas all glycosyltransferase toxins and effectors identified so far depend on the presence of divalent cations, LtpM is active in their absence. Proteins containing LtpM-like GT domains are encoded in the genomes of other L. pneumophila isolates and species, suggesting that LtpM is the first member of a novel family of glycosyltransferase effectors employed to subvert hosts.

Pubmed ID: 30573678

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: G1001729
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L018225/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/P028225/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/R010552/1

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

View all literature mentions

SMART (tool)

RRID:SCR_005026

Software tool for identification and annotation of genetically mobile domains and analysis of domain architectures.

View all literature mentions

Dictyostelium discoideum genome database (tool)

RRID:SCR_006643

Model organism database for the social amoeba Dictyostelium discoideum that provides the biomedical research community with integrated, high quality data and tools for Dictyostelium discoideum and related species. dictyBase houses the complete genome sequence, ESTs, and the entire body of literature relevant to Dictyostelium. This information is curated to provide accurate gene models and functional annotations, with the goal of fully annotating the genome to provide a ''''reference genome'''' in the Amoebozoa clade. They highlight several new features in the present update: (i) new annotations; (ii) improved interface with web 2.0 functionality; (iii) the initial steps towards a genome portal for the Amoebozoa; (iv) ortholog display; and (v) the complete integration of the Dicty Stock Center with dictyBase. The Dicty Stock Center currently holds over 1500 strains targeting over 930 different genes. There are over 100 different distinct amoebozoan species. In addition, the collection contains nearly 600 plasmids and other materials such as antibodies and cDNA libraries. The strain collection includes: * strain catalog * natural isolates * MNNG chemical mutants * tester strains for parasexual genetics * auxotroph strains * null mutants * GFP-labeled strains for cell biology * plasmid catalog The Dicty Stock Center can accept Dictyostelium strains, plasmids, and other materials relevant for research using Dictyostelium such as antibodies and cDNA or genomic libraries.

View all literature mentions

New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

View all literature mentions

Agilent Technologies (tool)

RRID:SCR_013575

Company provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.

View all literature mentions

RAW 264.7 (tool)

RRID:CVCL_0493

Cell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus

View all literature mentions

THP-1 (tool)

RRID:CVCL_0006

Cell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HeLa (tool)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

A-549 (tool)

RRID:CVCL_0023

Cell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions