PXD008701

PXD008701 is an original dataset announced via ProteomeXchange.

Title	Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis, part 2
Description	Aggregation is a sequence-specific process, nucleated by short aggregation prone regions (APR) that can be exploited to induce aggregation of proteins containing the same APR. Here we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Build-up of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates of E. coli and A. baumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy.
HostingRepository	PRIDE
AnnounceDate	2018-03-05
AnnouncementXML	Submission_2018-03-05_01:46:49.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD008701
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ladan Khodaparast
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-17 02:53:11	ID requested
⏵ 1	2018-03-05 01:46:51	announced

Khodaparast L, Khodaparast L, Gallardo R, Louros NN, Michiels E, Ramakrishnan R, Ramakers M, Claes F, Young L, Shahrooei M, Wilkinson H, Desager M, Mengistu Tadesse W, Nilsson KPR, Hammarstr, ö, m P, Aertsen A, Carpentier S, Van Eldere J, Rousseau F, Schymkowitz J, Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis. Nat Commun, 9(1):866(2018) [pubmed]

ProteomeXchange project tag: Protein Misfolding and Aggregation (B/D-HPP)

curator keyword: Biological

submitter keyword: inclusion bodies, Protein aggregation, E. coli, aggregation prone regions

Joost Schymkowitz
contact affiliation	Switch Laboratory (VIB-KU Leuven Center for Brain & Disease Research)-Department of Cellular and Molecular Medicine
contact email	joost.schymkowitz@kuleuven.vib.be
lab head
Ladan Khodaparast
contact affiliation	VIB‐KU Leuven Center for Brain & Disease Research Department of Cellular and Molecular Medicine
contact email	Ladan.khodaparast@kuleuven.vib.be
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/03/PXD008701

PRIDE project URI

• PRIDE
  1. PXD008701
     1. Label: PRIDE project
     2. Name: Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis, part 2