Membrane signaling complexes: Analysis, Synthesis and Control

Prof. Dr. Carola Hunte (Institute of Biochemistry and Molecular Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg)

Cellular signalling is mediated through protein assemblies of different complexity that operate as integrated circuits. The group pursues a structural biology approach to provide insights in architecture and organization principles of membrane signaling complexes for a better understanding of the mechanisms of signal transduction at and across membranes. This knowledge will pave the way to challenge and control signaling processes by synthetic approaches.

Here, we focus on membrane protein complexes that generate reactive oxygen species (ROS), which act as signaling molecules in the maintenance of physiological cell function and also cause oxidative damage in several human pathologies. Mitochondrial respiratory chain complexes I and III generate ROS as by-products of their enzymatic reaction mechanisms that are central for biological energy conversion. There is growing evidence that their ROS generation is tightly controlled and that these complexes may integrate energy and metabolic state for propagating this information in the cell. We will advance structural and functional studies on ROS generating complexes of the respiratory chain and on their supramolecular associations to elucidate how ROS production is controlled and linked to down-stream signalling processes on a molecular level. We employ a combined approach of biochemical and biophysical methods with emphasis on structural characterization by X-ray crystallography.

Selected Publications

Meisinger C, Hunte C (2017) Editorial: Recent Advances in Mitochondrial Biology – Integrated Aspects. Cell & Tiss. Res. 367, 1-3.

Kao W, Kleinschroth T, Nitschke W, Baymann F, Neehaul Y, Hellwig P, Richers S, Vonck J, Bott M, Hunte C (2016) The actinobacterial obligate respiratory supercomplex from Corynebacterium glutamicum. Biochim. Biophys. Acta 1857, 1705-1714

Zickermann V^#, Wirth C, Nasiri H, Siegmund K, Schwalbe H, Hunte C^#, Ulrich Brandt U^# (2015) Mechanistic Insight from the Crystal Structure of Mitochondrial Complex, Science 347, 44-49 (^#corresponding)      

Mir SH, Escher C, Kao WC, Birth D, Wirth C, Hunte C (2015) Generation of recombinant antibody fragments for membrane protein crystallization. Methods Enzym. 557, 201-218

Kao WC, Hunte C (2014) The molecular evolution of the Qo motif. Genome Biol. Evol. 6, 1894-1910

Birth D, Kao WC, Hunte C (2014) Structural analysis of atovaquone-inhibited cytochrome bc₁ complex reveals the molecular basis of antimalarial drug action. Nat. Comm. 5, 4029