title: Solution structure of the guanine nucleotide-binding STAS domain of SLC26-related SulP protein Rv1739c from Mycobacterium tuberculosis.
abstract: The structure and intrinsic activities of conserved STAS domains of the ubiquitous SulP/SLC26 anion transporter superfamily have until recently remained unknown. Here we report the heteronuclear, multidimensional NMR spectroscopy solution structure of the STAS domain from the SulP/SLC26 putative anion transporter Rv1739c of Mycobacterium tuberculosis. The 0.87-Å root mean square deviation structure revealed a four-stranded β-sheet with five interspersed α-helices, resembling the anti-σ factor antagonist fold. Rv1739c STAS was shown to be a guanine nucleotide-binding protein, as revealed by nucleotide-dependent quench of intrinsic STAS fluorescence and photoaffinity labeling. NMR chemical shift perturbation analysis partnered with in silico docking calculations identified solvent-exposed STAS residues involved in nucleotide binding. Rv1739c STAS was not an in vitro substrate of mycobacterial kinases or anti-σ factors. These results demonstrate that Rv1739c STAS binds guanine nucleotides at physiological concentrations and undergoes a ligand-induced conformational change but, unlike anti-σ factor antagonists, may not mediate signals via phosphorylation.
authors.affiliation: From the Divison of Molecular and Vascular Medicine,; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215 and.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215 and; Renal Division.
authors.forename: Liwen
authors.initials: L
authors.lastname: Ye
authors.affiliation: the Department of Molecular and Cell Biology, University of California, Berkeley, California 94720.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Baer
authors.affiliation: From the Divison of Molecular and Vascular Medicine,; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215 and.
authors.forename: Kumaran
authors.initials: K
authors.lastname: Shanmugasundaram
authors.affiliation: the Department of Molecular and Cell Biology, University of California, Berkeley, California 94720.
authors.forename: Tom
authors.initials: T
authors.lastname: Alber
authors.affiliation: From the Divison of Molecular and Vascular Medicine,; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215 and; Renal Division,. Electronic address: salper@bidmc.harvard.edu.
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.affiliation: From the Divison of Molecular and Vascular Medicine,; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215 and. Electronic address: arigby@bidmc.harvard.edu.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rigby
mesh_terms: D027321:Anion Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D027321:Anion Transport Proteins; D001426:Bacterial Proteins