PXD012180

PXD012180 is an original dataset announced via ProteomeXchange.

Title	Interaction of LipidII with specific residues of its extracytoplasmic domain governs appropriate localization and optimal activation of Mycobacterium tuberculosis PknB
Description	The Mycobacterium tuberculosis kinase PknB is essential for growth and survival of the pathogen in vitro and in vivo. Here we present the results of our efforts to elucidate the mechanism of regulation of PknB activity. The specific residues in the kinases’s extracytoplasmic domain that are essential for ligand interaction and survival of the bacterium have been identified. The extracytoplasmic domain interacts with mDAP-containing LipidII, and this is abolished upon mutation of the ligand-interacting residues. Abrogation of ligand-binding or sequestration of the ligand leads to aberrant localization of PknB. Contrary to the prevailing hypothesis, abrogation of ligand-binding is linked to activation loop hyperphosphorylation, and indiscriminate hyperphosphorylation of PknB substrates as well as other proteins, ultimately causing loss of homeostasis and cell death. We propose that the ligand-kinase interaction directs the appropriate localization of the kinase, coupled to stringently controlled activation of PknB., and consequently the downstream processes thereof.
HostingRepository	PRIDE
AnnounceDate	2019-03-14
AnnouncementXML	Submission_2019-04-03_04:35:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bolaji F Oyeyemi
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-24 02:29:04	ID requested
1	2019-03-14 06:21:27	announced
⏵ 2	2019-04-03 04:35:39	announced	Updated publication reference for PubMed record(s): 30874556.

Kaur P, Rausch M, Malakar B, Watson U, Damle NP, Chawla Y, Srinivasan S, Sharma K, Schneider T, Jhingan GD, Saini D, Mohanty D, Grein F, Nandicoori VK, LipidII interaction with specific residues of Mycobacterium tuberculosis PknB extracytoplasmic domain governs its optimal activation. Nat Commun, 10(1):1231(2019) [pubmed]

submitter keyword: PknB, PASTA, protein kinase, activation, substrate, mycobacteria, tuberculosis

Vinay K. Nandicoori
contact affiliation	Staff Scientist VII Signal Transduction Lab-1, National Institute of Immunology, Aruna Asaf Ali Marg New Delhi-110067
contact email	vinaykn@nii.ac.in
lab head
Bolaji F Oyeyemi
contact affiliation	International Center for Genetic Engineering and Biotechnology (ICGEB)
contact email	bolaji@icgeb.res.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012180
     1. Label: PRIDE project
     2. Name: Interaction of LipidII with specific residues of its extracytoplasmic domain governs appropriate localization and optimal activation of Mycobacterium tuberculosis PknB