title: Mycobacterium tuberculosis MtrAY102C is a gain-of-function mutant that potentially acts as a constitutively active protein.
abstract: The MtrAB histidine-aspartate signal transduction of mycobacteria includes the response regulator MtrA and sensor kinase MtrB. We recently showed that Mycobacterium smegmatis ΔmtrB is filamentous, defective for cell division, cell shape maintenance and shows compromised MtrA target gene expression. Interestingly, overproduction of phosphorylation competent M. tuberculosis MtrAY102C reverses the ΔmtrB mutant phenotype, although the genetic basis of phenotype reversal is unknown. Here we show that introduction of D56N mutation in MtrAY102C completely abolished its phosphorylation potential yet the double mutant protein retained a partial ability to reverse the mtrB mutant phenotype indicating that phosphorylation activity is not necessary for the function of MtrAY102C. The phosphorylation-defective MtrAD56N-Y102C protein bound its target promoters ripA and fbpB efficiently. Together, these results support a hypothesis that the gain-of-function phenotype of MtrAY102C is in part due to its ability to function as a constitutively active protein in the absence of phosphorylation.
authors.affiliation: Biomedical Research, The University of Texas Health Science Center @ Tyler, 11937 U.S. Hwy@ 271, Tyler, TX- 75708-3154, USA.
authors.forename: Akash T
authors.initials: AT
authors.lastname: Satsangi
authors.affiliation: Biomedical Research, The University of Texas Health Science Center @ Tyler, 11937 U.S. Hwy@ 271, Tyler, TX- 75708-3154, USA.
authors.forename: Emmanuel P
authors.initials: EP
authors.lastname: Pandeeti
authors.affiliation: Biomedical Research, The University of Texas Health Science Center @ Tyler, 11937 U.S. Hwy@ 271, Tyler, TX- 75708-3154, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Sarva
authors.affiliation: Biomedical Research, The University of Texas Health Science Center @ Tyler, 11937 U.S. Hwy@ 271, Tyler, TX- 75708-3154, USA.
authors.forename: Malini
authors.initials: M
authors.lastname: Rajagopalan
authors.affiliation: Biomedical Research, The University of Texas Health Science Center @ Tyler, 11937 U.S. Hwy@ 271, Tyler, TX- 75708-3154, USA. Electronic address: murty.madiraju@uthct.edu.
authors.forename: Murty V
authors.initials: MV
authors.lastname: Madiraju
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001216:Asparagine; D001224:Aspartic Acid; D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; C100938:MtrA protein, Bacteria; C079092:MtrB protein, Bacteria; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D001224:Aspartic Acid; D001216:Asparagine
keywords: Filamentation; Mycobacterium; Phenotype reversal; Phosphorylation; Response regulator