Structural insights into how metallochaperones UreE and UreG interact to deliver a toxic metal to urease.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Structural insights into how metallochaperones UreE and UreG interact to deliver a toxic metal to urease.
Συγγραφείς:	Chan CL; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Pang LTH; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Choi T; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Chan KC; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Tsang KL; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Lee KM; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Wong KB; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.
Πηγή:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2026 Sep 08; Vol. 123 (36), pp. e2535662123. Date of Electronic Publication: 2026 Sep 03.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Imprint Name(s):	Original Publication: Washington, DC : National Academy of Sciences
Ιατρικοί όροι (MeSH):	Urease/metabolism , Urease/chemistry , Nickel/metabolism , Nickel/chemistry , Metallochaperones/chemistry , Metallochaperones/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Helicobacter pylori/metabolism , Carrier Proteins/chemistry , Carrier Proteins/metabolism, Guanosine Triphosphate/metabolism ; Guanosine Triphosphate/chemistry ; Protein Binding ; Models, Molecular ; Crystallography, X-Ray ; Binding Sites ; Protein Conformation ; Phosphate-Binding Proteins
Περίληψη:	Maturation of urease, a virulence factor for Helicobacter pylori infection, requires the delivery of nickel ions to the metalloenzyme. To avoid cytotoxicity, Ni(II) ions are transferred within protein complexes of metallochaperones to ensure that the toxic metal does not escape into the cytoplasm. In the urease maturation pathway, metallochaperone UreG receives its Ni(II) ions by forming a 2:2 complex with another metallochaperone UreE. Using C-terminal truncation variants of UreE [UreE(1-158) and UreE(1-148)], we determined the crystal structures of the UreE2G2 complex bound with Ni(II) ions and GMPPNP, a nonhydrolyzable GTP analogue. UreE-UreG interactions are asymmetric, with the UreG dimer interacting mainly with the proximal UreE (closest to UreG). GTP binding induces conformational changes in the residues Asp37-Asp43 and the CPH motif (Cys66-Pro67-His68) of distal UreG that enable its anchorage to the UreE2G2 complex. His68 of distal UreG moves toward and chelates a Ni(II) ion at the UreE binding site. Formation of the UreE2G2 complex juxtaposes the Ni(II) binding sites of UreE and UreG. Supported by in vitro binding analyses, structural comparison suggests that nickel transfer from UreE to UreG induces conformational changes that weaken UreE-UreG interactions, thereby providing a mechanism for the dissociation of Ni(II)-bound UreG from the UreE2G2 complex. Our work presents a paradigm on how GTP and Ni(II) binding allosterically regulate the formation of a metallochaperone complex to facilitate nickel transfer.
Competing Interests:	Competing interests statement:The authors declare no competing interest.
Grant Information:	14117321 Research Grants Council, University Grants Committee (); 14117223 Research Grants Council, University Grants Committee (); C4041-18E Research Grants Council, University Grants Committee (); C4002-21-EF Research Grants Council, University Grants Committee (); C2003-22 W Research Grants Council, University Grants Committee (); AoE/M-403/16 Research Grants Council, University Grants Committee (); AoE/M-05/12 Research Grants Council, University Grants Committee ()
Contributed Indexing:	Keywords: Helicobacter pylori; metallochaperone; nickel; protein interaction; urease maturation
Substance Nomenclature:	EC 3.5.1.5 (Urease) 7OV03QG267 (Nickel) 0 (Metallochaperones) 0 (Bacterial Proteins) 0 (ureG protein, Bacteria) 0 (UreE protein, Bacteria) 0 (Carrier Proteins) 86-01-1 (Guanosine Triphosphate) 0 (Phosphate-Binding Proteins)
Entry Date(s):	Date Created: 20260903 Date Completed: 20260903 Latest Revision: 20260910
Update Code:	20260910
PubMed Central ID:	PMC13552852
DOI:	10.1073/pnas.2535662123
PMID:	42691087
Βάση Δεδομένων:	MEDLINE

Περιγραφή
ISSN:	1091-6490
DOI:	10.1073/pnas.2535662123