Crystal structure of Klebsiella aerogenes UreE, a nickel-binding metallochaperone for urease activation.
UreE is proposed to be a metallochaperone that delivers nickel ions to urease during activation of this bacterial virulence factor. Wild-type Klebsiella aerogenes UreE binds approximately six nickel ions per homodimer, whereas H144*UreE (a functional C-terminal truncated variant) was previously reported to bind two. We determined the structure of H144*UreE by multi-wavelength anomalous diffraction and refined it to 1.5 A resolution. The present structure reveals an Hsp40-like peptide-binding domain, an Atx1-like metal-binding domain, and a flexible C terminus. Three metal-binding sites per dimer, defined by structural analysis of Cu-H144*UreE, are on the opposite face of the Atx1-like domain than observed in the copper metallochaperone. One metal bridges the two subunits via the pair of His-96 residues, whereas the other two sites involve metal coordination by His-110 and His-112 within each subunit. In contrast to the copper metallochaperone mechanism involving thiol ligand exchanges between structurally similar chaperones and target proteins, we propose that the Hsp40-like module interacts with urease apoprotein and/or other urease accessory proteins, while the Atx1-like domain delivers histidyl-bound nickel to the urease active site.
Song
H K
HK
Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152, Planegg-Martinsried, Germany. hksong@red.dfci.harvard.edu
Mulrooney
S B
SB
Huber
R
R
Hausinger
R P
RP
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D021902:Enterobacter aerogenes / Q000737:chemistry*; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D009532:Nickel / Q000378:metabolism*; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry; D014510:Urease / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C090404:UreE protein, Bacteria; D003300:Copper; D009532:Nickel; D014510:Urease