PXD044892

PXD044892 is an original dataset announced via ProteomeXchange.

Title	Antimicrobial peptides of the apidaecin family inhibit the bacterial ribosome by multimodal mechanisms involving three different sites on the large ribosomal subunit
Description	Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial ribosomes by binding to the polypeptide exit tunnel (PET) near the peptidyl transferase center. Api137, an optimized derivative of honeybee apidaecin, traps the release factor (RF) at the ribosome, thereby arresting the ribosomes at stop codons. This study shows that Api137 occupies a second binding site near the exit of the PET and represses protein translation independently of RF1-trapping. Api88, the C-terminally amidated (-CONH2) analog of Api137 (-COOH), binds in a slightly shifted manner to the same regions without RF trapping, presumably by interfering with the translation process. Api88 also binds to a pocket deep within domain III of the 23S rRNA. In conclusion, Api88 and Api137 inhibit ribosomes through different multimodal mechanisms. These mechanisms have likely reduced the emergence of bacterial resistance and contributed to the evolutionary success of this structurally diverse group of PrAMPs, providing a promising pool for drug development efforts.
HostingRepository	PanoramaPublic
AnnounceDate	2024-06-02
AnnouncementXML	Submission_2024-06-02_08:15:22.863.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Daniela Volke
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	Deamidated; Oxidation
Instrument	SYNAPT G2-Si

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-27 16:39:58	ID requested
⏵ 1	2024-06-02 08:15:23	announced

Lauer SM, Reepmeyer M, Berendes O, Klepacki D, Gasse J, Gabrielli S, Grubm, ü, ller H, Bock LV, Krizsan A, Nikolay R, Spahn CMT, Hoffmann R, Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88. Nat Commun, 15(1):3945(2024) [pubmed]

submitter keyword: PrAMPs, 70S ribosome

Ralf Hoffmann
contact affiliation	Universität Leipzig
contact email	ralf.hoffmann@bbz.uni-leipzig.de
lab head
Daniela Volke
contact affiliation	Universität Leipzig
contact email	daniela.volke@bbz.uni-leipzig.de
dataset submitter

Panorama Public dataset URI