title: Imperfect coordination chemistry facilitates metal ion release in the Psa permease.
abstract: The relative stability of divalent first-row transition metal ion complexes, as defined by the Irving-Williams series, poses a fundamental chemical challenge for selectivity in bacterial metal ion acquisition. Here we show that although the substrate-binding protein of Streptococcus pneumoniae, PsaA, is finely attuned to bind its physiological substrate manganese, it can also bind a broad range of other divalent transition metal cations. By combining high-resolution structural data, metal-binding assays and mutational analyses, we show that the inability of open-state PsaA to satisfy the preferred coordination chemistry of manganese enables the protein to undergo the conformational changes required for cargo release to the Psa permease. This is specific for manganese ions, whereas zinc ions remain bound to PsaA. Collectively, these findings suggest a new ligand binding and release mechanism for PsaA and related substrate-binding proteins that facilitate specificity for divalent cations during competition from zinc ions, which are more abundant in biological systems.
authors.affiliation: 1] School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia. [2] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. [3].
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Couñago
authors.affiliation: 1] Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia. [2].
authors.forename: Miranda P
authors.initials: MP
authors.lastname: Ween
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Begg
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Megha
authors.initials: M
authors.lastname: Bajaj
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zuegg
authors.affiliation: 1] School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia. [2] School of Mathematics and Physics, University of Queensland, Brisbane, Australia.
authors.forename: Megan L
authors.initials: ML
authors.lastname: O'Mara
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.affiliation: 1] School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia. [2] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: McDevitt
mesh_terms: D001665:Binding Sites; D002412:Cations; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D008958:Models, Molecular; D013296:Streptococcus pneumoniae / Q000378:metabolism
chemical_list: D002412:Cations; D026901:Membrane Transport Proteins; D008670:Metals