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Project C

Project C




Prof. Dr. B. Brenner



Department of Molecular and Cell Physiology







Research focus:

Myosins represent a super-family of proteins which together with the Kinesins and Dyneins are responsible for essentially all forms of motile functions in living cells. This includes muscle contraction, movement of flagellae, fast axonal transport in neurons, transport of vesicles and organelles, etc.


In our laboratory we mainly concentrate on myosins. Our goals are to understand the molecular mechanisms by which force and movement are generated in muscle, as well as understanding the mechanisms of vesicle transport by non-muscle myosins or kinesins.



Studies on demembranated muscle fibers


To understand the functional relevance of the various structural domains of the myosin molecule we make use of point mutations which were identified in patients with familial hypertrophic cardiomyopathy. Detailed comparison of a large variety of mechanical, biochemical and structural parameters allows us to identify the primary functional changes associated with these point mutations (1).


To develop a detailed understanding of the molecular processes underlying regulation of muscular function, we have developed procedures to exchange wildtype regulatory proteins (troponin, tropomyosin) for fluorescently labeled, wildtype and mutant proteins in demembranated muscle fibers. With this approach we can collect both structural and kinetic data about the movements of the regulatory proteins and their relevance for different steps in regulation (2,3).


Single molecule microscopy


To analyse the function of muscle and non-muscle myosins as well as kinesins we established techniques that allow to observe forces and movements generated by individual myosin or kinesin molecules (4) and to relate these to the binding and dissociation of individual, fluorescently labeled nucleotide molecules (ATP, ADP, nucleotide analogs) visualized as individual molecules in an evanescent field microscope (5).


Group members:

Prof. Dr. B. Brenner

PD. Dr. T. Kraft

B. Piep

P. Uta

C. v. Grumbkow

E. Mählmann

T. Mattei

T. Scholz

J. Köhler

G. Lübbe



Mechanical, biochemical and x-ray diffraction studies on demembranated muscle fibers.


Protein exchange in demembranated muscle fibers, analysis via confocal microscopy and fluorescence spectroscopy.


Single molecule fluorescence observed with an evanescent field microscope including FRET and fluorescence polarisation (binding/dissociation of ligands, substrates, products).


Recording of forces and movements of single molecules by microneedle/laser trap or systems developed from atomic force microscopy (AFM).


Key References:

  1. Köhler J, Winkler G, Schulte I, Scholz T, McKenna W, Brenner B, Kraft T. Mutation of the myosin converter domain alters cross-bridge elasticity. Proc Natl Acad Sci USA (in press).

  2. Brenner B, Kraft T, Yu LC, Chalovich JM. Thin filament activation probed by fluorescence of N-((2-Iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole-labelled troponin I incorporated in skinned fibers of rabbit psoas muscle. Biophys J 1999;77: 2677-91.

  3. Brenner B., Chalovich JM. Kinetics of Thin Filament Activation Probed by Fluorescence of N-((2-Iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole-labelled Troponin I Incorporated in Skinned Fibers of Rabbit Psoas Muscle. Implications for Regulation of Muscle Contraction. Biophys J 1999; 77: 2692-708.

  4. Ruff C, Furch M, Brenner B, Manstein D, Meyhöfer E. Single-molecule tracking of myosins with genetically engineered amplifier domains. Nature Struct Biol 2001; 8: 226-9.

  5. Brenner B, Kojima H. Effect of actin on ATP-hydrolysis of individual myosin molecules studied with evanescent-field microscopy. Biophys J 2001; 80: 579a.

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