PXD034240

PXD034240 is an original dataset announced via ProteomeXchange.

Title	A Legionella toxin mimics tRNA and glycosylates the translation machinery to trigger a ribosome-associated stress response
Description	Pathogenic microorganisms often secrete proteins or nucleic acids that mimic the structure and/or function of molecules expressed within their host counterparts. This molecular mimicry empowers pathogens to target and subvert critical host processes and helps establish their infectious paradigm. We report here that the intracellular bacterium Legionella pneumophila (L.p.) secretes a toxin named SidI (substrate of icm/dot transporter I) which possesses a transfer RNA (tRNA) like fold and functions as a mannosyl transferase enzyme. The 3.1 Å cryo-EM structure of SidI reveals an N-terminal domain that exhibits a characteristic ‘inverted L-shape’ and charge conservation that is present in two known protein mimics of tRNAs, the bacterial elongation factor EF-G and the mammalian release factor eRF1. In addition, SidI’s C-terminal domain adopts a glycosyl transferase B fold and shares considerable homology to a known mannosyl transferase. This molecular coupling of fold and enzymatic function allows SidI to bind to and enzymatically modify components of the host translational apparatus, including the ribosome, resulting in a robust block of protein synthesis that is comparable to the potency exhibited by the toxin ricin. Additionally, we uncovered that the translational pausing activated by SidI elicits a stress response signature that is highly similar to one activated by elongation inhibitors that target the ribosome and induce ribosome collisions. SidI-mediated perturbations to the ribosome activate the stress kinases ZAKα and p38, that in turn drive the accumulation of the protein activating transcription factor 3 (ATF3). Intriguingly, ATF3 escapes the translation block imposed by SidI, translocates to the nucleus, and subsequently orchestrates the transcription of stress-inducible genes that culminates in the activation of a cell death program. Thus, using Legionella and its effectors as tools, we have unravelled the role of a ribosome to nuclear signaling pathway that regulates cell fate.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:53:47.588.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Danielle Swaney
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-01 03:55:23	ID requested
1	2023-07-12 11:56:22	announced
⏵ 2	2024-10-22 05:53:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Legionella

Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
lab head
Danielle Swaney
contact affiliation	UCSF
contact email	daniswan@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034240
     1. Label: PRIDE project
     2. Name: A Legionella toxin mimics tRNA and glycosylates the translation machinery to trigger a ribosome-associated stress response