Struktur und Funktion der Häm a Synthase CtaA und von Surf1 als Biogenese-Chaperon für die Cytochrom c Oxidase

• Antragsteller: Professor Dr. Clemens Glaubitz; Professor Dr. Bernd Ludwig; Professor Dr. Klaas Martinus Pos
• Fachliche Zuordnung: Biochemie
• Förderung: Förderung von 2011 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 206409571

• Erstellungsjahr: 2016

Zusammenfassung der Projektergebnisse

Cytochrome c oxidase, a multi-subunit integral membrane protein complex of mitochondria, houses several metal and heme cofactors involved in internal redox steps. The aim of this project was to address its biogenesis using a simpler bacterial model system by following the transfer pathway for heme a starting from its site of synthesis, heme a synthase, via the membrane-bound chaperone Surf1c, eventually to oxidase subunit I. Surf1c has been shown both in vivo and in vitro to interact with the synthase, thereby specifically taking up the heme cofactor in an orientation suitable for transfer to its binding pocket(s) in oxidase subunit I. Using biochemical approaches, we have been able to obtain new insights concerning the sequence of binding between CtaA and Surf1c during COX biogenesis. In order to relate these data to structural information, extensive crystallisation screens and solid-state NMR studies were carried out on Surf1c. Unfortunately, despite significant efforts, Surf1c resolutely resisted structural investigations.

Projektbezogene Publikationen (Auswahl)

• Characterization of heme binding properties of Paracoccus denitrificans Surf1 proteins. FEBS-J. 278, 1769-1778 (2011)
  Hannappel, Achim, Freya Alena Bundschuh, and Bernd Ludwig
  
• Role of Surf1 in heme recruitment for bacterial oxidase biogenesis. Biochim.Biophys.Acta Bioenerg. Special Issue Biogenesis 1817, 928-937 (2012)
  Hannappel, Achim, Freya Alena Bundschuh, and Bernd Ludwig
  
• Deciphering protein-protein interactions during the biogenesis of cytochrome c oxidase from Paracoccus denitrificans. FEBS-J 282, 537 - 549 (2015)
  Gurumoorthy, Priya and Bernd Ludwig
  (Siehe online unter https://doi.org/10.1111/febs.13160)
• Protein chaperones mediating copper insertion into the CuA site of the aa 3-type cytochrome c oxidase of Paracoccus denitrificans Biochim.Biophys.Acta Bioenerg. 1847, 202-211 (2015)
  Dash, Banaja Priyadarshini, Melanie Alles, Freya Alena Bundschuh, Oliver-M.H. Richter, and Bernd Ludwig
  (Siehe online unter https://doi.org/10.1016/j.bbabio.2014.11.001)