PXD008587

PXD008587 is an original dataset announced via ProteomeXchange.

Title	Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis
Description	Tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection remains a huge global public health problem. One striking characteristic of Mtb is its ability to adapt to hypoxia, and thus ensuing transition to dormant state for persistent infection, but how the hypoxia responses of Mtb is regulated remains largely unknown. Here, we performed a quantitative acetylome analysis to compare the acetylation profile of Mtb under aeration and hypoxia, and showed that 377 acetylation sites in 269 proteins of Mtb were significantly change under hypoxia. Especially, deacetylation of Dormancy Survival Regulator (DosR) at K182 promoted the hypoxia response of Mtb and enhanced transcription of DosR-targeted genes. Mechanistically, recombinant DosRK182R protein demonstrated enhanced DNA-binding activity in comparison with DosRK182Q protein. Moreover, Rv0998 was identified as an acetyltransferase that mediates the acetylation of DosR at K182. Deletion of Rv0998 also promoted the adaption of Mtb to hypoxia and transcription of DosR-targeted genes. Mice infected with Mtb strain containing acetylation-defective DosRK182R or lacking Rv0998 had much lower bacterial counts, and less severe histopathological impairments compared with those infected with the wild-type strain. Our findings suggest that hypoxia induces the deacetylation of DosR, which in turn increases its DNA binding ability to promote the transcription of target genes, allowing Mtbto transit to dormancy under hypoxia.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:12:55.066.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rachel Green
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-03 01:31:29	ID requested
1	2018-10-22 09:13:22	announced
⏵ 2	2024-10-22 04:12:55	announced	2024-10-22: Updated project metadata.

Yang H, Sha W, Liu Z, Tang T, Liu H, Qin L, Cui Z, Chen J, Liu F, Zheng R, Huang X, Wang J, Feng Y, Ge B, Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis. Emerg Microbes Infect, 7(1):34(2018) [pubmed]

10.1038/s41426-018-0032-2;

curator keyword: Biomedical

submitter keyword: Lysine acetylation

Mtb;DosR

Hypoxia growth;DNA binding

Baoxue Ge
contact affiliation	Shanghai Key Laboratory of Tuberculosis, Clinic and Research Center of Tuberculosis,Shanghai Pulmonary Hospital, Tongji University School of Medicine
contact email	baoxue_ge@tongji.edu.cn
lab head
Rachel Green
contact affiliation	PTM Biolabs Inc.
contact email	xuan_mao@ptm-biolab.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008587
     1. Label: PRIDE project
     2. Name: Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis