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Disulfide driven folding for a conditionally disordered protein.
Fraga, Hugo; Pujols, Jordi; Gil-Garcia, Marcos; Roque, Alicia; Bernardo-Seisdedos, Ganeko; Santambrogio, Carlo; Bech-Serra, Joan-Josep; Canals, Francesc; Bernadó, Pau; Grandori, Rita; Millet, Oscar; Ventura, Salvador.
Affiliation
  • Fraga H; Institut de Biotecnologia i Biomedicina. Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Pujols J; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Gil-Garcia M; Departamento de Bioquimica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
  • Roque A; Institut de Biotecnologia i Biomedicina. Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Bernardo-Seisdedos G; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Santambrogio C; Institut de Biotecnologia i Biomedicina. Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Bech-Serra JJ; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Canals F; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
  • Bernadó P; Protein Stability and Inherited Diseases Laboratory, CIC bioGUNE, 48160, Derio, Spain.
  • Grandori R; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.
  • Millet O; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Ventura S; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Sci Rep ; 7(1): 16994, 2017 12 05.
Article in En | MEDLINE | ID: mdl-29208936
ABSTRACT
Conditionally disordered proteins are either ordered or disordered depending on the environmental context. The substrates of the mitochondrial intermembrane space (IMS) oxidoreductase Mia40 are synthesized on cytosolic ribosomes and diffuse as intrinsically disordered proteins to the IMS, where they fold into their functional conformations; behaving thus as conditionally disordered proteins. It is not clear how the sequences of these polypeptides encode at the same time for their ability to adopt a folded structure and to remain unfolded. Here we characterize the disorder-to-order transition of a Mia40 substrate, the human small copper chaperone Cox17. Using an integrated real-time approach, including chromatography, fluorescence, CD, FTIR, SAXS, NMR, and MS analysis, we demonstrate that in this mitochondrial protein, the conformational switch between disordered and folded states is controlled by the formation of a single disulfide bond, both in the presence and in the absence of Mia40. We provide molecular details on how the folding of a conditionally disordered protein is tightly regulated in time and space, in such a way that the same sequence is competent for protein translocation and activity.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carrier Proteins / Protein Folding / Mitochondrial Membrane Transport Proteins / Disulfides / Intrinsically Disordered Proteins Limits: Humans Language: En Journal: Sci Rep Year: 2017 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carrier Proteins / Protein Folding / Mitochondrial Membrane Transport Proteins / Disulfides / Intrinsically Disordered Proteins Limits: Humans Language: En Journal: Sci Rep Year: 2017 Document type: Article Affiliation country: