PXD065790

PXD065790 is an original dataset announced via ProteomeXchange.

Title	AuxB interacts directly with GpsB and PknB to coordinate cell envelope processes that contribute to intrinsic antibiotic resistance in Staphylococcus aureus
Description	Staphylococcus aureus, a leading cause of serious infections, produces various factors important for intrinsic resistance to antibiotics. Understanding what intrinsic resistance factors do may enable strategies to potentiate existing antibiotics. The membrane protein AuxB is an intrinsic resistance factor that helps S. aureus withstand diverse compounds that target the cell envelope, but its cellular functions are unknown. We show here that AuxB is a four-pass transmembrane protein with an intracellular C-terminus that interacts directly with the cytosolic cell cycle regulator GpsB. We also show AuxB’s membrane domain forms a homodimer that exists in equilibrium with a heterodimer of AuxB and PknB, a eukaryotic-like serine/threonine kinase that has been implicated in cell envelope processes. Shifting the equilibrium to favor AuxB-bound PknB impairs growth on tunicamycin, a condition where PknB is essential, which suggests that AuxB binding antagonizes a PknB function. To link PknB’s domains to compound susceptibility phenotypes, we assessed the fitness of PknB variants under several conditions. We find that PknB’s extracellular and kinase domains are not functionally inter-dependent but instead play distinct roles in withstanding cell envelope stress. AuxB evidently antagonizes functions of PknB’s extracellular PASTA domain, the presence of which is beneficial under tunicamycin treatment regardless of whether the kinase domain is active. On compounds where the PASTA domain is deleterious, increasing the amount of AuxB-bound PknB can also ameliorate sensitivity. Collectively, our data suggest that AuxB, as a homodimer and through its interactions with GpsB and PknB, modulates cell envelope processes during cell growth and division.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-25_09:15:44.711.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-04 07:00:55	ID requested
⏵ 1	2025-08-25 09:15:45	announced

Dataset with its publication pending

submitter keyword: PrkA, PrkC, PASTA domain, Staphylococcus aureus,serine/threonine kinases, cell wall,PknB, cell envelope, StkP, antibiotic resistance

Suzanne Walker
contact affiliation	Department of Microbiology Blavatnik Institute Harvard Medical School Boston, Massachusetts 02115,USA
contact email	suzanne_walker@hms.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065790
     1. Label: PRIDE project
     2. Name: AuxB interacts directly with GpsB and PknB to coordinate cell envelope processes that contribute to intrinsic antibiotic resistance in Staphylococcus aureus