title: Insights into the mode of action of a putative zinc transporter CzrB in Thermus thermophilus.
abstract: The crystal structures of the cytoplasmic domain of the putative zinc transporter CzrB in the apo and zinc-bound forms reported herein are consistent with the protein functioning in vivo as a homodimer. NMR, X-ray scattering, and size-exclusion chromatography provide support for dimer formation. Full-length variants of CzrB in the apo and zinc-loaded states were generated by homology modeling with the Zn2+/H+ antiporter YiiP. The model suggests a way in which zinc binding to the cytoplasmic fragment creates a docking site to which a metallochaperone can bind for delivery and transport of its zinc cargo. Because the cytoplasmic domain may exist in the cell as an independent, soluble protein, a proposal is advanced that it functions as a metallochaperone and that it regulates the zinc-transporting activity of the full-length protein. The latter requires that zinc binding becomes uncoupled from the creation of a metallochaperone-docking site on CzrB.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Cherezov
authors.forename: Nicole
authors.initials: N
authors.lastname: Höfer
authors.forename: Doletha M E
authors.initials: DM
authors.lastname: Szebenyi
authors.forename: Olga
authors.initials: O
authors.lastname: Kolaj
authors.forename: J Gerard
authors.initials: JG
authors.lastname: Wall
authors.forename: Richard
authors.initials: R
authors.lastname: Gillilan
authors.forename: Vasundara
authors.initials: V
authors.lastname: Srinivasan
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Jaroniec
authors.forename: Martin
authors.initials: M
authors.lastname: Caffrey
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D016963:Thermus thermophilus / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C120279:CzrB protein, bacteria; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C017800:zinc-binding protein; D015032:Zinc
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