Crystal Structure Determination and Functional Characterization of the Metallochaperone SlyD from Thermus thermophilus

Löw, Christian; Neumann, Piotr; Tidow, Henning; Weininger, Ulrich; Haupt, Caroline; Friedrich-Epler, Beatrice; Schölz, Christian; Stubbs, Milton T.; Balbach, Jochen

doi:10.1016/j.jmb.2010.03.014

Cited by 58 publications

(107 citation statements)

References 79 publications

(101 reference statements)

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“…Three-dimensional modeling of BPSS1823 indicated that the structure is highly conserved (Fig. 1B) and that all of the amino acids that are believed to contribute most significantly to enzyme activity are present (3,7,21,29) These observations were confirmed by nuclear magnetic resonance (NMR) and X-ray determination of the structure of BPSS1823 (34a). These observations strongly suggest that BPSS1823 is a functional orthologue of Mip.…”

Section: Discussionmentioning

confidence: 78%

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A Burkholderia pseudomallei Macrophage Infectivity Potentiator-Like Protein Has Rapamycin-Inhibitable Peptidylprolyl Isomerase Activity and Pleiotropic Effects on Virulence

et al. 2011

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Macrophage infectivity potentiators (Mips) are a group of virulence factors encoded by pathogenic bacteria such as Legionella, Chlamydia, and Neisseria species. Mips are part of the FK506-binding protein (FKBP) family, whose members typically exhibit peptidylprolyl cis-trans isomerase (PPIase) activity which is inhibitable by the immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization of BPSS1823, a Mip-like protein in the intracellular pathogen Burkholderia pseudomallei. Recombinant BPSS1823 protein has rapamycin-inhibitable PPIase activity, indicating that it is a functional FKBP. A mutant strain generated by deletion of BPSS1823 in B. pseudomallei exhibited a reduced ability to survive within cells and significant attenuation in vivo, suggesting that BPSS1823 is important for B. pseudomallei virulence. In addition, pleiotropic effects were observed with a reduction in virulence mechanisms, including resistance to host killing mechanisms, swarming motility, and protease production.

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Section: Discussionmentioning

confidence: 78%

“…BPSS1823 does not contain a putative N-terminal dimerization domain but has high homology to the C-terminal PPIase domain possessed by other Mips, suggesting that it could have PPIase activity. In addition, BPSS1823 possesses most residues required for PPIase activity in human FKBP12 (3,21,29).…”

Section: Burkholderia Pseudomallei Encodes a Mip-like Proteinmentioning

confidence: 99%

A Burkholderia pseudomallei Macrophage Infectivity Potentiator-Like Protein Has Rapamycin-Inhibitable Peptidylprolyl Isomerase Activity and Pleiotropic Effects on Virulence

et al. 2011

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“…15,16 SlyD is a member of this family and is present among all prokaryotes. 17 It consists of two structurally well-separated domains: the N-terminal prolyl isomerase domain of FKBP type with the second domain integrated in the FKBP flap ("inserted-inflap" (IF) domain) 14,18,19 and an unstructured Cterminal tail of variable length, rich in cysteine and histidine residues with high affinity to metal ions. The chaperone activity resides in the IF domain because deletion of that domain results in loss of this activity.…”

Section: Introductionmentioning

confidence: 99%

“…The chaperone activity resides in the IF domain because deletion of that domain results in loss of this activity. 18,19 Compared to related FKBP prolyl isomerases and to the isolated FKBP domain, the PPIase activity of SlyD is enhanced by a factor of about 100 in the presence of the chaperone domain. 15,16,19 It was hypothesized that the coupled transfer of substrate proteins bound at the chaperone domain to the PPIase domain could be responsible for this increase in PPIase activity.…”

Section: Introductionmentioning

confidence: 99%

Conformational Plasticity and Dynamics in the Generic Protein Folding Catalyst SlyD Unraveled by Single-Molecule FRET

Kahra

Kovermann

Löw

et al. 2011

Journal of Molecular Biology

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“…Proteins known as "metallochaperones" play key roles in this process. Although a few structures of the metallochaperone have now been determined (1)(2)(3)(4)(5)(6), the molecular mechanisms underlying specific metal transfers remain unclear with the exception of the metallochaperone involved in the copper transport to superoxide dismutase (1).…”

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confidence: 99%

A Molecular Mechanism for Copper Transportation to Tyrosinase That Is Assisted by a Metallochaperone, Caddie Protein

Matoba

Bando

Oda

et al. 2011

Journal of Biological Chemistry

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The Cu(II)-soaked crystal structure of tyrosinase that is present in a complex with a protein, designated "caddie," which we previously determined, possesses two copper ions at its catalytic center. We had identified two copper-binding sites in the caddie protein and speculated that copper bound to caddie may be transported to the tyrosinase catalytic center. In our present study, at a 1.16 -1.58 Å resolution, we determined the crystal structures of tyrosinase complexed with caddie prepared by altering the soaking time of the copper ion and the structures of tyrosinase complexed with different caddie mutants that display little or no capacity to activate tyrosinase. Based on these structures, we propose a molecular mechanism by which two copper ions are transported to the tyrosinase catalytic center with the assistance of caddie acting as a metallochaperone.Among the many biological systems that employ transition metal ions for their function, it is a requirement that specific metal co-factors be transported into the correct metalloenzyme. Proteins known as "metallochaperones" play key roles in this process. Although a few structures of the metallochaperone have now been determined (1-6), the molecular mechanisms underlying specific metal transfers remain unclear with

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Crystal Structure Determination and Functional Characterization of the Metallochaperone SlyD from Thermus thermophilus

Cited by 58 publications

References 79 publications

A Burkholderia pseudomallei Macrophage Infectivity Potentiator-Like Protein Has Rapamycin-Inhibitable Peptidylprolyl Isomerase Activity and Pleiotropic Effects on Virulence

A Burkholderia pseudomallei Macrophage Infectivity Potentiator-Like Protein Has Rapamycin-Inhibitable Peptidylprolyl Isomerase Activity and Pleiotropic Effects on Virulence

Conformational Plasticity and Dynamics in the Generic Protein Folding Catalyst SlyD Unraveled by Single-Molecule FRET

A Molecular Mechanism for Copper Transportation to Tyrosinase That Is Assisted by a Metallochaperone, Caddie Protein

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