Max Planck Institute of Biophysics

Frankfurt am Main, Germany

Max Planck Institute of Biophysics

Frankfurt am Main, Germany

The Max Planck Institute for Biophysics is located in Frankfurt am Main, Germany. It was founded as Kaiser Wilhelm Institute for Biophysics in 1937, and moved into a new building in 2003. It is one of 80 institutes in the Max Planck Society .A prerequisite for the understanding of the fundamental processes of life is the knowledge of the structure of the participating macromolecules. Two of the four departments are devoted to the challenging task of determining the structure of membrane proteins. Under the direction of Hartmut Michel , the Department of Molecular Membrane Biology approaches this problem primarily by x-ray crystallography, whereas the Department of Structural Biology, headed by Werner Kühlbrandt, uses the complementary technique of electron microscopy. The Department of Biophysical Chemistry, directed by Ernst Bamberg, studies the function of these proteins in native or reconstituted membranes by electrophysiological and spectroscopic methods. The fourth department "Molecular Neurogenetics" under the direction of Peter Mombaerts has started its work in 2007. Since 2007, the institute hosts two Max-Planck Research Groups: "Computational Structural Biology", led by Lucy R. Forrest, and "Theoretical Molecular Biophysics", directed by José D. Faraldo-Gómez.Since April 2003, the institute's four departments are housed in the same building, resulting in improved scientific interaction between the research groups. Scientific links to fellow researchers at Frankfurt University have been strengthened further as the institute is now situated next to the University's biology, chemistry and physics laboratories.Together with the Max Planck Institute for Brain Research and the Goethe University of Frankfurt am Main the institute runs the International Max Planck Research School on the Structure and Function of Biological Membranes, a graduate program offering a Ph.D. Wikipedia.

SEARCH FILTERS
Time filter
Source Type

Schlegel K.,Goethe University Frankfurt | Leone V.,Max Planck Institute of Biophysics | Faraldo-Gomez J.D.,Max Planck Institute of Biophysics | Muller V.,Goethe University Frankfurt
Proceedings of the National Academy of Sciences of the United States of America | Year: 2012

ATP synthases are the primary source of ATP in all living cells. To catalyze ATP synthesis, these membrane-associated complexes use a rotary mechanism powered by the transmembrane diffusion of ions down a concentration gradient. ATP synthases are assumed to be driven either by H + or Na +, reflecting distinct structural motifs in their membrane domains, and distinct metabolisms of the host organisms. Here, we study the methanogenic archaeon Methanosarcina acetivorans using assays of ATP hydrolysis and ion transport in inverted membrane vesicles, and experimentally demonstrate that the rotary mechanism of its ATP synthase is coupled to the concurrent translocation of both H + and Na + across the membrane under physiological conditions. Using free-energy molecular simulations, we explain this unprecedented observation in terms of the ion selectivity of the binding sites in the membrane rotor, which appears to have been tuned via amino acid substitutions so that ATP synthesis in M. acetivorans can be driven by the H + and Na +gradients resulting from methanogenesis. We propose that this promiscuity is a molecular mechanism of adaptation to life at the thermodynamic limit.


Perez C.,Max Planck Institute of Biophysics | Koshy C.,Max Planck Institute of Biophysics | Yildiz O.,Max Planck Institute of Biophysics | Ziegler C.,Max Planck Institute of Biophysics | Ziegler C.,University of Regensburg
Nature | Year: 2012

Betaine and Na + symport has been extensively studied in the osmotically regulated transporter BetP from Corynebacterium glutamicum, a member of the betaine/choline/carnitine transporter family, which shares the conserved LeuT-like fold of two inverted structural repeats. BetP adjusts its transport activity by sensing the cytoplasmic K + concentration as a measure for hyperosmotic stress via the osmosensing carboxy-terminal domain. BetP needs to be in a trimeric state for communication between individual protomers through several intratrimeric interaction sites. Recently, crystal structures of inward-facing BetP trimers have contributed to our understanding of activity regulation on a molecular level. Here we report new crystal structures, which reveal two conformationally asymmetric BetP trimers, capturing among them three distinct transport states. We observe a total of four new conformations at once: an outward-open apo and an outward-occluded apo state, and two closed transition states - one in complex with betaine and one substrate-free. On the basis of these new structures, we identified local and global conformational changes in BetP that underlie the molecular transport mechanism, which partially resemble structural changes observed in other sodium-coupled LeuT-like fold transporters, but show differences we attribute to the osmolytic nature of betaine, the exclusive substrate specificity and the regulatory properties of BetP. © 2012 Macmillan Publishers Limited. All rights reserved.


Lam R.S.,Max Planck Institute of Biophysics | Mombaerts P.,Max Planck Institute of Biophysics
European Journal of Neuroscience | Year: 2013

The mammalian olfactory system has developed some functionality by the time of birth. There is behavioral and limited electrophysiological evidence for prenatal olfaction in various mammalian species. However, there have been no reports, in any mammalian species, of recordings from prenatal olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) gene. Here we have performed patch-clamp recordings from mouse OSNs that express the OR gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral, respectively. We found that, out of a combined total of 20 OSNs from embryos of these two strains at embryonic day (E)16.5 or later, all responded to a cognate odorous ligand. By contrast, none of six OSNs responded to the ligand at E14.5 or E15.5. The kinetics of the odorant-evoked electrophysiological responses of prenatal OSNs are similar to those of postnatal OSNs. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally, but the axon terminals of OSNs expressing these OR genes may be synaptically active in the olfactory bulb at embryonic stages. The upper limit of the acquisition of odorant responsiveness for S1 and MOR23 OSNs at E16.5 is consistent with the developmental expression patterns of components of the olfactory signaling pathway. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.


Best R.B.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Hummer G.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Hummer G.,Max Planck Institute of Biophysics | Eaton W.A.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

The recent availability of long equilibrium simulations of protein folding in atomistic detail for more than 10 proteins allows us to identify the key interactions driving folding. We find that the collective fraction of native amino acid contacts, Q, captures remarkably well the transition states for all the proteins with a folding free energy barrier. Going beyond this global picture, we devise two different measures to quantify the importance of individual interresidue contacts in the folding mechanism: (i) the log-ratio of lifetimes of contacts during folding transition paths and in the unfolded state and (ii) a Bayesian measure of how predictive the formation of each contact is for being on a transition path. Both of these measures indicate that native, or near-native, contacts are important for determining mechanism, as might be expected. More remarkably, however, we found that for almost all the proteins, with the designed protein 3D being a notable exception, nonnative contacts play no significant part in determining folding mechanisms.


Khan M.,Max Planck Institute of Biophysics | Vaes E.,Max Planck Institute of Biophysics | Mombaerts P.,Max Planck Institute of Biophysics
Cell | Year: 2011

Each olfactory sensory neuron (OSN) in mouse chooses one of 1,200 odorant receptor (OR) genes for expression. OR genes are chosen for expression by greatly varying numbers of OSNs. The mechanisms that regulate the probability of OR gene choice remain unclear. Here, we have applied the NanoString platform of fluorescent barcodes and digital readout to measure RNA levels of 577 OR genes in a single reaction, with probes designed against coding sequences. In an inbred mouse strain with a targeted deletion in the P element, we find that this element regulates OR gene choice differentially across its cluster of 24 OR genes. Importantly, the fold changes of NanoString counts in ΔP or ΔH mice are in very close agreement with the fold changes of cell counts, determined by in situ hybridization. Thus, the P and H elements regulate the probability of OR gene choice, not OR transcript level per OSN. © 2011 Elsevier Inc.


Kuhlbrandt W.,Max Planck Institute of Biophysics
EMBO Journal | Year: 2016

Sodium channels are central to a host of fundamental cellular processes, including sensory perception, pain, and muscle contraction. In order to understand any of these processes in detail, it is necessary to know the atomic structure of the channel proteins both with and without bound sodium ions. In this issue, Naylor et al (2016) present the structure of a bacterial sodium channel tetramer. The three bound, partially hydrated sodium ions line up neatly in a row inside the selectivity filter, providing us with the first detailed insights into ion conduction in sodium channels, and the mechanisms by which sodium and potassium ions are discriminated. © 2016 EMBO.


Okazaki K.-I.,Max Planck Institute of Biophysics | Hummer G.,Max Planck Institute of Biophysics
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

We combine molecular simulations and mechanical modeling to explore the mechanism of energy conversion in the coupled rotary motors of FoF1-ATP synthase. A torsional viscoelastic model with frictional dissipation quantitatively reproduces the dynamics and energetics seen in atomistic molecular dynamics simulations of torquedriven γ-subunit rotation in the F1-ATPase rotary motor. The torsional elastic coefficients determined from the simulations agree with results from independent single-molecule experiments probing different segments of the γ-subunit, which resolves a long-lasting controversy. At steady rotational speeds of ~1 kHz corresponding to experimental turnover, the calculated frictional dissipation of less than kBT per rotation is consistent with the high thermodynamic efficiency of the fully reversible motor. Without load, the maximum rotational speed during transitions between dwells is reached at ~1 MHz. Energetic constraints dictate a unique pathway For the coupled rotations of the Fo and F1 rotary motors in ATP synthase, and explain the need For the finer stepping of the F1 motor in the mammalian system, as seen in recent experiments. Compensating For incommensurate eightfold and threefold rotational symmetries in Fo and F1, respectively, a significant fraction of the external mechanical work is transiently stored as elastic energy in the γ-subunit. The general framework developed here should be applicable to other molecular machines.


Marinelli F.,Max Planck Institute of Biophysics
Biophysical Journal | Year: 2013

In this work a new method for the automatic exploration and calculation of multidimensional free energy landscapes is proposed. Inspired by metadynamics, it uses several collective variables that are relevant for the investigated process and a bias potential that discourages the sampling of already visited configurations. The latter potential allows escaping a local free energy minimum following the direction of slow motions. This is different from metadynamics in which there is no specific direction of the biasing force and the computational effort increases significantly with the number of collective variables. The method is tested on the Ace-Ala3-Nme peptide, and then it is applied to investigate the Trp-cage folding mechanism. For this protein, within a few hundreds of nanoseconds, a broad range of conformations is explored, including nearly native ones, initiating the simulation from a completely unfolded conformation. Finally, several folding/unfolding trajectories give a systematic description of the Trp-cage folding pathways, leading to a unified view for the folding mechanisms of this protein. The proposed mechanism is consistent with NMR chemical shift data at increasing temperature and recent experimental observations pointing to a pivotal role of secondary structure elements in directing the folding process toward the native state. © 2013 Biophysical Society.


Preiss L.,Max Planck Institute of Biophysics
PLoS biology | Year: 2010

We solved the crystal structure of a novel type of c-ring isolated from Bacillus pseudofirmus OF4 at 2.5 A, revealing a cylinder with a tridecameric stoichiometry, a central pore, and an overall shape that is distinct from those reported thus far. Within the groove of two neighboring c-subunits, the conserved glutamate of the outer helix shares the proton with a bound water molecule which itself is coordinated by three other amino acids of outer helices. Although none of the inner helices contributes to ion binding and the glutamate has no other hydrogen bonding partner than the water oxygen, the site remains in a stable, ion-locked conformation that represents the functional state present at the c-ring/membrane interface during rotation. This structure reveals a new, third type of ion coordination in ATP synthases. It appears in the ion binding site of an alkaliphile in which it represents a finely tuned adaptation of the proton affinity during the reaction cycle.


Allegretti M.,Max Planck Institute of Biophysics | Klusch N.,Max Planck Institute of Biophysics | Mills D.J.,Max Planck Institute of Biophysics | Vonck J.,Max Planck Institute of Biophysics | And 2 more authors.
Nature | Year: 2015

ATP, the universal energy currency of cells, is produced by F-type ATP synthases, which are ancient, membrane-bound nanomachines. F-type ATP synthases use the energy of a transmembrane electrochemical gradient to generate ATP by rotary catalysis. Protons moving across the membrane drive a rotor ring composed of 8-15 c-subunits1. A central stalk transmits the rotation of the c-ring to the catalytic F1 head, where a series of conformational changes results in ATP synthesis2. A key unresolved question in this fundamental process is how protons pass through the membrane to drive ATP production. Mitochondrial ATP synthases form V-shaped homodimers in cristae membranes3. Here we report the structure of a native and active mitochondrial ATP synthase dimer, determined by single-particle electron cryomicroscopy at 6.2 Å resolution. Our structure shows four long, horizontal membrane-intrinsic α-helices in the a-subunit, arranged in two hairpins at an angle of approximately 70° relative to the c-ring helices. It has been proposed that a strictly conserved membrane-embedded arginine in the a-subunit couples proton translocation to c-ring rotation4. A fit of the conserved carboxy-terminal a-subunit sequence places the conserved arginine next to a proton-binding c-subunit glutamate. The map shows a slanting solvent-accessible channel that extends from the mitochondrial matrix to the conserved arginine. Another hydrophilic cavity on the lumenal membrane surface defines a direct route for the protons to an essential histidine-glutamate pair5. Our results provide unique new insights into the structure and function of rotary ATP synthases and explain how ATP production is coupled to proton translocation. ©2015 Macmillan Publishers Limited. All rights reserved.

Loading Max Planck Institute of Biophysics collaborators
Loading Max Planck Institute of Biophysics collaborators