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Werner Kühlbrandt

Max Planck Institute of Biophysics, Department of Structural Biology, Frankfurt, Germany

Werner Kühlbrandt studied chemistry and crystallography at the Free University Berlin, and biochemistry and biophysics at King’s College London. He did his PhD with Nigel Unwin at the MRC Laboratory of Molecular Biology in Cambridge, UK, investigating the structure of two-dimensional ribosome crystals by electron microscopy. He turned to structural studies of membrane proteins as a postdoc, first at the ETH Zürich, and then at Imperial College London. After a short stay at UC Berkeley, CA, he became a group leader at the EMBL Heidelberg in 1988. Since 1997 he is a director at the Max Planck Institute of Biophysics in Frankfurt, Germany, where his department of Structural Biology studies the structure and mechanisms of membrane proteins by X-ray and electron crystallography, single-particle cryo-EM, electron tomography and biophysical methods.


Mechanistic insights from high-resolution cryoEM structures of ATP synthases

With the ongoing resolution revolution in electron cryo-microscopy (cryoEM), large and dynamic membrane protein complexes have become accessible to high-reso­lution structural studies. We have used single-particle cryoEM to determine the structure of the complete, monomeric ATP synthase (cF1Fo) from spinach chloroplasts at up to 2.9 Å, and of the dimeric mitochondrial F1FATP synthase (mtF1Fo) from the green alga Polytomella at around 2.7 Å resolution. Bound nucleotides with their coordinating Mg ions and water molecules are resolved in cF1. The two-domain subunit δ of cF1F(OSCP in mitochondria) joins the three α-subunits of the Fhead to the peripheral stalk in three different ways. Three resolved rotary states of cF1Findicate that the peripheral stalk flexes to store torsional energy, whereas subunit γ of the central stalk works as a rigid body. In both mitochondria and chloroplasts, subunit in the membrane-embedded Fmotor forms two aqueous channels to conduct protons to and from the protonation sites on the c-ring rotor that powers ATP generation. The channels and the polar and charged sidechains that define them in the hydrophobic membrane interior are conserved over an evolutionary distance of around 1.5 billion years. The Fmotor assembly with its hairpin of long, membrane-embedded subunit helices adapts equally well to the 10-subunit c-ring of mtF1Fand the 14-subunit c-ring of cF1Fo. Electron cryo-tomography of chloroplast thylakoids indicated that cF1Fis always monomeric, whereas all mtF1Fdimers form rows that impose high local membrane curvature on the inner membrane. When reconstituted into proteoliposomes, yeast and Polytomella ATP synthase dimers assemble into rows spon­taneously, inducing high local membrane curvature as in mitochondria.