PXD002144

PXD002144 is an original dataset announced via ProteomeXchange.

Title	Label-free quantitative proteomics reveals a role for the Mycobacterium tuberculosis SecA2 pathway in exporting solute binding proteins and Mce transporters to the cell wall
Description	Mycobacterium tuberculosis is an example of a bacterial pathogen with a specialized SecA2-dependent protein export system that contributes to its virulence. Our understanding of the mechanistic basis of SecA2-dependent export and the role(s) of the SecA2 pathway in M. tuberculosis pathogenesis has been hindered by our limited knowledge of the proteins exported by the pathway. Here, we set out to identify M. tuberculosis proteins that use the SecA2 pathway for their export from the bacterial cytoplasm to the cell wall. Using label-free quantitative (LFQ) proteomics involving spectral counting, we compared the cell wall and cytoplasmic proteomes of wild type M. tuberculosis to that of a ΔsecA2 mutant. This work revealed a role for the M. tuberculosis SecA2 pathway in the cell wall localization of solute binding proteins (SBPs) that work with ABC transporters to import solutes. Another discovery was a profound effect of SecA2 on the cell wall localization of the Mce1 and Mce4 lipid transporters, which contribute to M. tuberculosis virulence. In addition to the effects on SBP and Mce transporter export, our LFQ analysis revealed an unexpected relationship between SecA2 and the hypoxia-induced DosR regulon, which is associated with M. tuberculosis latency. Nearly half of the transcriptionally controlled DosR regulon of cytoplasmic proteins were detected at higher levels in the ΔsecA2 mutant versus wild type M. tuberculosis. By increasing the list of M. tuberculosis proteins known to be affected by the SecA2 pathway, this study expands our appreciation of the types of proteins exported by this pathway and guides our understanding of the mechanism of SecA2-dependent protein export in mycobacteria. At the same time, the newly identified SecA2-dependent proteins are helpful for understanding the significance of this pathway to M. tuberculosis virulence and physiology
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_09:44:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kate Zulauf
SpeciesList	scientific name: Mycobacterium tuberculosis H37RvAE; NCBI TaxID: 757417;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-05-06 00:45:27	ID requested
⏵ 1	2018-10-24 09:44:56	announced

Feltcher ME, Gunawardena HP, Zulauf KE, Malik S, Griffin JE, Sassetti CM, Chen X, Braunstein M, Label-free Quantitative Proteomics Reveals a Role for the Mycobacterium tuberculosis SecA2 Pathway in Exporting Solute Binding Proteins and Mce Transporters to the Cell Wall. Mol Cell Proteomics, 14(6):1501-16(2015) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Mycobacterium tuberculosis, SecA2, LC-MS/MS, Spectral Counting

Miriam Braunstein
contact affiliation	Microbiology and Immunology UNC Chapel Hill Chapel Hill, NC USA
contact email	braunste@med.unc.edu
lab head
Kate Zulauf
contact affiliation	UNC Chapel Hill
contact email	kzulauf@email.unc.edu
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/2018/10/PXD002144

PRIDE project URI

• PRIDE
  1. PXD002144
     1. Label: PRIDE project
     2. Name: Label-free quantitative proteomics reveals a role for the Mycobacterium tuberculosis SecA2 pathway in exporting solute binding proteins and Mce transporters to the cell wall