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Karim Fahmy Group

Structural basis of biological switches and biomolecular recognition

Portrait Karim Fahmy

Structural changes in biopolymers are the basis of the regulation of their biological function. Exposure of specific sites for molecular recognition as well as switching processes between states of different activity of a biomolecule can thus be accomplished. Understanding the underlying mechanisms allows identifying putative sites for pharmacological intervention and opens the prospect of engineering artificial molecular switches. We are interested in the mechanisms and dynamics of such structural transitions which we study in real time, using vibrational spectroscopy, circular dichroism and fluorescence spectroscopy. Our lab has thus made major contributions to the mechanistic characterization of G-protein-coupled receptors (GPCRs). We are currently exploring the role of water as a dynamic structural component by expressing membrane proteins with engineered fluorescence labels that report intra-membrane protein water. In combination with calorimetric studies we aim at the integration of structural and thermodynamic data. In the same manner, we have identified fundamental principles that determine stability and dynamics of synthetic DNA superstructures, so-called DNA origami.  The ensemble of our studies provides, reaction models that describe both structural and energetic aspects of conformational changes in natural and synthetic biopolymers.

Future Projects and Goals

We are extending our research on lipid-protein interactions to live-cell monitoring of the influence of the plasma membrane lipidome on cell metabolism. Using  isothermal microcalorimetry, the metabolic heat flow of microorganisms, including Mycoplasma-derived “minimal cells”, is studied in dependence on lipid compositions and other factors. We develop mathematical models and open-source software to analyze such data from which fundamental conclusions can be drawn on energy fluxes in microbial physiology.

Methodological and Technical Expertise

  • spectroscopy of structural transitions  in recombinant proteins
  • Fourier Transform Infrared (FTIR) Spectroscopy
  • Circular Dichroism (CD) Spectroscopy
  • Static and Time-Resolved Fluorescence
  • Differential Scanning Calorimetry (DSC)
  • Isothermal Titration Calorimetry (ITC)
  • calorimetry for systemsbiology

CV

since 2002
Head of the Biophysics Division at the Forschungszentrum Dresden-Rossendorf (FZD)

1994–2002
Habilitation, University Freiburg

1991–1994
Postdoctoral Howard Hughes Medical Institute Fellow at Rockefeller University, New York

1991
PhD, University Freiburg, Hans-Griesebach-Award

More Information

www.hzdr.de

Selected Publications

Lehmann, N., Alexiev, U. & K. Fahmy
Linkage between the intramembrane H-bond network around aspartic acid 83 and the cytosolic environment of helix 8 in photoactivated rhodopsin.
J. Mol. Biol. 366:1129–1141. (2007)

Madathil, S., Furlinski, G. & K. Fahmy
Structure and pH-Sensitivity of the Transmembrane Segment 3 of Rhodopsin.
Biopolymers 82:329–333. (2006)

Fahmy, K., Merroun, M., Pollmann, K., Raff, J., Savchuk, O., Hennig, C., Selenska-Pobell, S.
Secondary structure and Pd(II) coordination in S-layer proteins from Bacillus sphaericus studied by infrared and X-ray absorption spectroscopy.
Biophys. J. 91:996–1007. (2006)

Breitinger, U., Breitinger, H-G., Bauer, F., Fahmy, K., Glockenhammer, D. & C.-M. Becker
Conserved high-affinity ligand binding and membrane association in the native and refolded extracellular domain of the human glycine receptor α1 subunit.
J. Biol. Chem. 279: 1627–1636. (2004)

Lehmann, N., Krishna Aradhyam, G.K. & K. Fahmy
Suramin affects coupling of rhodopsin to transducin.
Biophys. J. 82: 793–802. (2002)

Contact

Helmholtz-Zentrum Dresden-Rossendorf (HZDR)
Institute of Radiochemistry
Bautzner Landstraße 400
01328 Dresden, Germany