Functional Determinants of Metal Ion Transport and Selectivity in Paralogous Cation Diffusion Facilitator Transporters CzcD and MntE in Streptococcus pneumoniae

Journal of Bacteriology
Julia E Martin, David P Giedroc

Abstract

Cation diffusion facilitators (CDFs) are a large family of divalent metal transporters that collectively possess broad metal specificity and contribute to intracellular metal homeostasis and virulence in bacterial pathogens. Streptococcus pneumoniae expresses two homologous CDF efflux transporters, MntE and CzcD. Cells lacking mntE or czcD are sensitive to manganese (Mn) or zinc (Zn) toxicity, respectively, and specifically accumulate Mn or Zn, respectively, thus suggesting that MntE selectively transports Mn, while CzcD transports Zn. Here, we probe the origin of this metal specificity using a phenotypic growth analysis of pneumococcal variants. Structural homology to Escherichia coli YiiP predicts that both MntE and CzcD are dimeric and each protomer harbors four pairs of conserved metal-binding sites, termed the A site, the B site, and the C1/C2 binuclear site. We find that single amino acid mutations within both the transmembrane domain A site and the B site in both CDFs result in a cellular metal sensitivity similar to that of the corresponding null mutants. However, multiple mutations in the predicted cytoplasmic C1/C2 cluster of MntE have no impact on cellular Mn resistance, in contrast to the analogous substitutions in ...Continue Reading

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Citations

Jan 28, 2017·Molecular Microbiology·Julia E MartinDavid P Giedroc
Oct 20, 2017·International Journal of Molecular Sciences·Taiho KambeTaka-Aki Takeda
Feb 15, 2018·The Journal of Biological Chemistry·Rilee ZeinertLauren S Waters
Jul 11, 2018·Metallomics : Integrated Biometal Science·Charles E Zogzas, Somshuvra Mukhopadhyay
Jun 6, 2019·Nucleic Acids Research·Julia E MartinDavid P Giedroc
Jan 29, 2017·The Journal of Physiological Sciences : JPS·Takafumi HaraToshiyuki Fukada
Apr 17, 2019·Acta Crystallographica. Section D, Structural Biology·Camila A CotrimDavid Drew
Nov 12, 2017·Scientific Reports·Emily C FarthingLorraine E Williams
Jul 28, 2016·The Journal of Biological Chemistry·Daiana A CapdevilaDavid P Giedroc
Aug 8, 2021·Science Advances·Stephanie L NevilleChristopher A McDevitt
Oct 10, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lingfang ZhuXihui Shen

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