Academic Journal

How protein-protein interaction and conformational changes mediate nickel incorporation in urease maturation

Bibliographic Details
Title: How protein-protein interaction and conformational changes mediate nickel incorporation in urease maturation
Contributors: Nim, Yap Shing (author.), Wong, Kam Bo (thesis advisor.), Chinese University of Hong Kong Graduate School. Division of Life Sciences. (degree granting institution.)
Publication Year: 2019
Collection: The Chinese University of Hong Kong: CUHK Digital Repository / 香港中文大學數碼典藏
Subject Terms: Urease--Analysis, Protein-protein interactions, Nickel, Protein Interaction Mapping, Protein Interaction Maps
Description: Ph.D. ; Urease catalyzes the degradation of urea into ammonia and carbon dioxide. It is important for nitrogen metabolism in many organisms, except mammals. It is also a virulence factor of gastric pathogen Helicobacter pylori. Urease in general has a bi-nickel catalytic centre, which requires a set of accessory proteins to maturate, namely UreE, UreF, UreG and UreH (or UreD in other species). UreE is known to be a nickel chaperone receiving nickel(II) ion from the [NiFe]-hydrogenase pathway. The nickel is passed from UreE to UreG in the GTP-bound UreE₂G₂ complex. UreG forms UreG₂F₂H₂ complex with GDP. Upon GTP/Ni binding, UreG dimerizes and dissociates from UreG₂F₂H₂. After GTP hydrolysis, UreG turns back to monomer and releases the nickel. This work reports two structures: Ni/GMPPNP-bound UreG and UreD/apo-urease from Klebsiella pneumoniae. By structural comparison, conformational changes on UreG and apo-urease were identified. This work proves the presence of the GTPdependent conformational changes of UreG, and it provides a molecular mechanism of the switching of UreG between UreE₂ and UreF₂H₂ controlled by GTP binding/hydrolysis cycle. Conformational changes on apo-urease upon UreD-binding was shown to be essential for their interaction and urease maturation. Preliminary analysis also suggested those changes create tunnels in apo-urease connecting the one in UreD. It provided a mechanism of the delivery of toxic nickel inside the protein complex UreD/apo-urease. H. pylori urease was found to have two forms: trimer and dodecamer. A new purification method was developed to separate them. H. pylori urease trimer was discovered to be unable to interact with UreFH and be activated, in contrast to the dodecamer. It is speculated that the two urease oligomers may have conformational differences that relate to the significance of this special urease dodecamer in H. pylori. In short, this work provided evidence on how ligand-protein interaction or protein-protein interaction would change the conformation of a ...
Document Type: text
File Description: electronic resource; remote; 1 online resource (157 leaves) : illustrations (some color); computer; online resource
Language: English
Chinese
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https://repository.lib.cuhk.edu.hk/en/item/cuhk-2398982
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  Label: Title
  Group: Ti
  Data: How protein-protein interaction and conformational changes mediate nickel incorporation in urease maturation
– Name: Author
  Label: Contributors
  Group: Au
  Data: Nim, Yap Shing (author.)<br />Wong, Kam Bo (thesis advisor.)<br />Chinese University of Hong Kong Graduate School. Division of Life Sciences. (degree granting institution.)
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2019
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: The Chinese University of Hong Kong: CUHK Digital Repository / 香港中文大學數碼典藏
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  Data: <searchLink fieldCode="DE" term="%22Urease--Analysis%22">Urease--Analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Protein-protein+interactions%22">Protein-protein interactions</searchLink><br /><searchLink fieldCode="DE" term="%22Nickel%22">Nickel</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Interaction+Mapping%22">Protein Interaction Mapping</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Interaction+Maps%22">Protein Interaction Maps</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Ph.D. ; Urease catalyzes the degradation of urea into ammonia and carbon dioxide. It is important for nitrogen metabolism in many organisms, except mammals. It is also a virulence factor of gastric pathogen Helicobacter pylori. Urease in general has a bi-nickel catalytic centre, which requires a set of accessory proteins to maturate, namely UreE, UreF, UreG and UreH (or UreD in other species). UreE is known to be a nickel chaperone receiving nickel(II) ion from the [NiFe]-hydrogenase pathway. The nickel is passed from UreE to UreG in the GTP-bound UreE₂G₂ complex. UreG forms UreG₂F₂H₂ complex with GDP. Upon GTP/Ni binding, UreG dimerizes and dissociates from UreG₂F₂H₂. After GTP hydrolysis, UreG turns back to monomer and releases the nickel. This work reports two structures: Ni/GMPPNP-bound UreG and UreD/apo-urease from Klebsiella pneumoniae. By structural comparison, conformational changes on UreG and apo-urease were identified. This work proves the presence of the GTPdependent conformational changes of UreG, and it provides a molecular mechanism of the switching of UreG between UreE₂ and UreF₂H₂ controlled by GTP binding/hydrolysis cycle. Conformational changes on apo-urease upon UreD-binding was shown to be essential for their interaction and urease maturation. Preliminary analysis also suggested those changes create tunnels in apo-urease connecting the one in UreD. It provided a mechanism of the delivery of toxic nickel inside the protein complex UreD/apo-urease. H. pylori urease was found to have two forms: trimer and dodecamer. A new purification method was developed to separate them. H. pylori urease trimer was discovered to be unable to interact with UreFH and be activated, in contrast to the dodecamer. It is speculated that the two urease oligomers may have conformational differences that relate to the significance of this special urease dodecamer in H. pylori. In short, this work provided evidence on how ligand-protein interaction or protein-protein interaction would change the conformation of a ...
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  Data: Use of this resource is governed by the terms and conditions of the Creative Commons "Attribution-NonCommercial-NoDerivatives 4.0 International" License (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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RecordInfo BibRecord:
  BibEntity:
    Languages:
      – Text: English
      – Text: Chinese
    Subjects:
      – SubjectFull: Urease--Analysis
        Type: general
      – SubjectFull: Protein-protein interactions
        Type: general
      – SubjectFull: Nickel
        Type: general
      – SubjectFull: Protein Interaction Mapping
        Type: general
      – SubjectFull: Protein Interaction Maps
        Type: general
    Titles:
      – TitleFull: How protein-protein interaction and conformational changes mediate nickel incorporation in urease maturation
        Type: main
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          Name:
            NameFull: Nim, Yap Shing (author.)
      – PersonEntity:
          Name:
            NameFull: Wong, Kam Bo (thesis advisor.)
      – PersonEntity:
          Name:
            NameFull: Chinese University of Hong Kong Graduate School. Division of Life Sciences. (degree granting institution.)
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          Dates:
            – D: 01
              M: 01
              Type: published
              Y: 2019
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