PXD009239

PXD009239 is an original dataset announced via ProteomeXchange.

Title	Two faces of an essential PknB substrate in mycobacteria
Description	Tuberculosis claims nearly 2 million lives annually and its causative agent Mycobacterium tuberculosis is a highly successful pathogen which explores multiple signalling mechanisms to grow and survive in humans for decades. Well-studied protein kinase B (PknB), one of the 11 serine/threonine kinases present in M. tuberculosis, is critical for growth in vitro and in vivo. Here we demonstrate that PknB-depleted mycobacteria can normally replicate and synthesise peptidoglycan in osmoprotective medium. Comparative phosphoproteomics of PknB-producing and PknB-depleted mycobacteria identifies CwlM as a major PknB substrate. Complementation studies of cwlM mutant further support CwlM phosphorylation as the molecular basis for the PknB essentiality. We demonstrate that in growing mycobacteria CwlM is produced in two forms with distinct functions which are essential for growth: a non-phosphorylated membrane-associated CwlM and a PknB-phosphorylated cytoplasmic CwlM. Immunoprecipitation and mycobacterial two hybrid assays reveal partner proteins for phosphorylated and non-phosphorylated CwlM forms, as FhaA, a forkhead-associated domain protein, and MurJ (MviN), a predicted Lipid II flippase, respectively. We propose that PknB is not required for mycobacterial division but coordinates peptidoglycan polymerization and cross-linking by a novel CwlM-mediated mechanism
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:43:58.956.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009239
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andrew Bottrill
SpeciesList	scientific name: Mycobacterium tuberculosis complex; NCBI TaxID: NCBITaxon:77643; scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationList	Ammonia-loss; Phospho; Dehydrated; Oxidation; Acetyl; Carbamidomethyl
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-16 07:45:16	ID requested
1	2018-09-24 06:33:55	announced
2	2019-06-17 03:25:19	announced	Updated publication reference for PubMed record(s): 30282038.
⏵ 3	2024-10-22 04:44:07	announced	2024-10-22: Updated project metadata.

10.6019/PXD009239;

10.1016/j.celrep.2018.09.004;

Turapov O, Forti F, Kadhim B, Ghisotti D, Sassine J, Straatman-Iwanowska A, Bottrill AR, Moynihan PJ, Wallis R, Barthe P, Cohen-Gonsaud M, Ajuh P, Vollmer W, Mukamolova GV, Two Faces of CwlM, an Essential PknB Substrate, in Mycobacterium tuberculosis. Cell Rep, 25(1):57-67.e5(2018) [pubmed]

curator keyword: Biological

submitter keyword: Mycobacterium tuberculosis, PASTA domain, CwlM, PknB, MurJ, peptidoglycan, phosphoproteomics, serine/threonine protein kinase

Galina Mukamolova
contact affiliation	Leicester Tuberculosis Research Group Department of Infection, Immunity and Inflammation University of Leicester Leicester LE1 9HN United Kingdom
contact email	gvm4@le.ac.uk
lab head
Andrew Bottrill
contact affiliation	University of Warwick
contact email	a.r.bottrill@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009239
     1. Label: PRIDE project
     2. Name: Two faces of an essential PknB substrate in mycobacteria