title: Biochemical characterization of the histidine triad protein PhtD as a cell surface zinc-binding protein of pneumococcus.
abstract: Zinc homeostasis is critical for pathogen host colonization. Indeed, during invasion, Streptococcus pneumoniae has to finely regulate zinc transport to cope with a wide range of Zn(2+) concentrations within the various host niches. AdcAII was identified as a pneumococcal Zn(2+)-binding protein; its gene is present in an operon together with the phtD gene. PhtD belongs to the histidine triad protein family, but to date, its function has not been clarified. Using several complementary biochemical methods, we provide evidence that like AdcAII, PhtD is a metal-binding protein specific for zinc. When Zn(2+) binds (K(d) = 131 ± 10 nM), the protein displays substantial thermal stabilization. We also present the first direct evidence of a joint function of AdcAII and PhtD by demonstrating that their expression is corepressed by Zn(2+), that they interact directly in vitro, and that they are colocalized at the bacterial surface. These results suggest the common involvement of the AdcAII-PhtD system in pneumococcal zinc homeostasis.
authors.affiliation: CEA, Institut de Biologie Structurale Jean-Pierre Ebel, Grenoble, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Loisel
authors.forename: Suneeta
authors.initials: S
authors.lastname: Chimalapati
authors.forename: Catherine
authors.initials: C
authors.lastname: Bougault
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Benoit
authors.initials: B
authors.lastname: Gallet
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Di Guilmi
authors.forename: Jeremy
authors.initials: J
authors.lastname: Brown
authors.forename: Thierry
authors.initials: T
authors.lastname: Vernet
authors.forename: Claire
authors.initials: C
authors.lastname: Durmort
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008074:Lipoproteins; D011994:Recombinant Proteins; C097552:histidine triad protein; C017800:zinc-binding protein; D006867:Hydrolases; D015032:Zinc