Max Planck Institute of Biophysics
Yearbook entries


  • Electron cryo-microscopy of membrane protein complexes

    2019 Kühlbrandt, Werner
    Single-particle electron cryo-microscopy (CryoEM) is ideal for determining the high-resolution structure membrane protein complexes that are too unstable or too dynamic for x-ray crystallography. Intact rotary ATPases have resisted crystallization for more than 40 years. However, central aspects of their mechanisms now have become clear thanks to the recent CryoEM based structures of intact, functional ATP synthases. The two best and most informative of these structures, the chloroplast ATP synthase and a mitochondrial ATP synthase dimer, have been shown by our department.


  • Acyl-CoA dehydrogenase/electron-transferring flavoprotein complexes: Structural determinants of a flavin-based electron bifurcation

    2018 Kayastha, Kanwal; Demmer, Julius K.; Müller, Volker; Buckel, Wolfgang; Ermler, Ulrich
    Flavin-based electron bifurcating (FBEB) enzyme complexes play a vital role in obligate anaerobic microorganisms for increasing the efficiency of their energy metabolism. They drive an endergonic reduction by an exergonic one via the same electron donor. The energy coupling is realized by a reduced flavin which transfers via energy splitting one strongly and one weakly reducing electron to two different substrates. How FBEB enzyme complexes are structurally constructed is outlined using the example of two acyl-CoA dehydrogenase/electron-transferring flavoproteins.


  • Molecular mechanisms of lipid membrane shaping and quality control

    2017 Hummer, Gerhard
    Living cells are coated and structured by lipid membranes. We addressed two important questions: how are membranes shaped into their often unusual forms, and how do cells monitor the membrane state? With molecular and coarse-grained simulations, we could show how the proteins Mga2 and Ire1 can sense the state of the endoplasmic reticulum. Also, new insights have been obtained about the fusion of vesicles, the formation of tubular structures in the endoplasmic reticulum, and the induction of autophagosomes aided by the Atg1 complex.


  • Structure of dimeric ATP synthase from the inner membrane of yeast mitochondria

    2016 Hahn, Alexander; Parey, Kristian; Bublitz, Maike; Mills, Deryck J.; Zickermann, Volker; Vonck, Janet; Kühlbrandt, Werner; Meier, Thomas
    We determined the structure of a complete, dimeric F1Fo-ATP synthase from mitochondria of the yeast Yarrowia lipolytica by a combination of cryo-electron microscopy (cryo-EM) and X-ray crystallography. The structure resolves 58 of the 60 subunits in the dimer. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Our data explain the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology.


  • How nature reduces molecular oxygen to water conserving energy at the same time

    2015 Michel, Hartmut; Ermler, Ulrich; Safarian, Schara
    Molecular oxygen appeared in the atmosphere about three billion years ago. Nature developed two membrane integrated enzymatic systems which reduce oxygen to water and use the energy of this reaction to produce biologically important energy carriers. These enzymes are the haem-copper terminal oxidases, e.g. cytochrome c oxidase, and the bd oxidases. The atomic structures of representative members of both enzyme families were determined. These evolutionary unrelated enzymes apparently use the same mechanisms to conserve energy and to prevent the formation of toxic reactive oxygen species.


  • Molecular Simulations: from biomolecular structures to function

    2014 Hummer, Gerhard
    Molecular simulations allow us to study the functional mechanisms of biomolecules. Thanks to their enormously detailed description, by resolving the motion of every atom, such simulations help to interpret complex experiments. Simulations also allow us to venture into areas which are difficult to access by experiments, such as the detailed characterization of enzymatic reaction mechanisms. Moreover, by “watching proteins at work”, new and fundamental processes can be discovered by using molecular simulations.


  • A truly selfish gene and its supporters

    2013 Herrmann, Bernhard G.
    At fertilisation, we get one set of chromosomes from each parent and, in general, pass on either the paternal or the maternal allele of each gene with equal frequency to our children. This has been taught by Mendel. According to Richard Dawkins’ hypothesis, however, there are selfish genes which are not content with random selection and thus actively promote their increased transmission to the next generation. Evidence for this assumption comes from a mouse gene that is transmitted at a frequency of up to 99% from males to their offspring.
  • Novel systems biology research for a personalized medicine in cancer

    2013 Nietfeld, Wilfried; Lehrach, Hans
    The solution of many medically important aspects depends on the prediction of the behaviour of complex networks, e.g. biological networks active within a tumor but also in other tissues of a patient under complex conditions, for example a particular therapy. So far, it is not possible to predict the success of a specific therapy for a specific patient. We are sequencing the genome of individual cancer patients as well as the genome and transcriptome of their tumor as a basis of a virtual-patient-model, used to predict effect and side effects of specific therapies on the individual patient.
  • Current Research in Structural Biology

    2013 Werner Kühlbrandt
    The Department elucidates the structure and function of membrane proteins as well as macromolecular protein complexes by using electron microscopy, x-ray crystallography, biochemical and biophysical methods. It consists of a group lead by director Werner Kühlbrandt and project groups operated by Janet Vonck and Özkan Yildiz. Thomas Meier and Daniel Rhinow run two independent research groups. Christine Ziegler, now appointed as professor at the University of Regensburg, is still associated with the Department. Here, we present current data and results from all over the Department’s research.


  • Nutrigenomics: natural modulation of gene expression

    2012 Sauer, Sascha
    The scientific focus of the research group lies on the systematic analysis of the modulation of gene and protein expression. This process can be specifically influenced by the interaction of genes and natural products, which are e.g. derived from food. We analyse if and by which mechanisms natural products interfere with genes or gene products. The interdisciplinary approach comprises basic and applied research. The results can be useful for optimised application of natural products to improve various metabolic processes.
  • Better late than never: Genome research turns to rare diseases

    2012 Ropers, Hans-Hilger
    For more than 15 years, genome research has looked for clinically relevant genetic risk factors for common diseases, with meagre results. Now rare disorders come into focus of genome research worldwide. Scientists at the Department of Human Molecular Genetics have successfully dealt with rare genetic disorders for many years. Since the introduction of novel, affordable sequencing techniques it has become possible, in principle, to elucidate the molecular causes of all single gene disorders, with far-reaching consequences for diagnosis, prevention and therapy.
  • GcpE and LytB: Enzymes of isoprenoid biosynthesis as targets for drugs against malaria and tuberculosis

    2012 Rekittke, Ingo; Jomaa, Hassan; Ermler, Ulrich
    Isoprenoids are involved in vital processes of all organisms. Their biosynthesis proceeds via two C5-building blocks, which are produced dependent on the organism either by the mevalonate- or the desoxyxylose (DOXP) pathway. The DOXP pathway is used by various human pathogens but not by man and therefore provides an attractive target for anti-infectious agents, e.g., against malaria and tuberculosis.


  • Neurodegenerative disorders – from yeast to neurodegenerative processes

    2011 Krobitsch, Sylvia
    Late onset neurodegenerative disorders are progressive disorders, which usually strike during mid-age of affected individuals and with age result in profound neuronal degeneration. Even though these diseases are quite common worldwide, the mechanisms responsible for their pathogenesis are, in most cases, poorly understood, and effective preventative therapies for these devastating disorders are currently not at hand.
  • Optogenetics: The molecular basis and applications

    2011 Bamberg, Ernst
    The new field of optogenetics describes mainly the use of the light-gated ion channel, Channelrhodopsin 2 (ChR2) and of the light-driven Cl-pump Halorhodopsin (NphR) for stimulation and silencing of neurons simply by light in cultured cells as well as in brains of living animals. In order to increase the possibilities of application we have focused our research to develop new and improved tools.


  • Give me five! Or six? Or seven?

    2010 Kuss, Pia
    Give me five, high five, hello and good bye - all shown to others with one hand. Certainly everyone knows that this hand comprises five digits. But not everyone is born with exactly five digits. In humans, occasionally hereditary skeletal limb malformations do occur. One malformation, the so-called synpolydactyly, implies that patients are born with additional digits, and those are fused above all. This phenotype develops due to a mutation within the Hoxd13 gene, leading to a lack of retinoic acid and thereby causing uncontrolled cartilage production at wrong sites in the extremity.
  • Protein networks: How protein interactions define shape and function of cells

    2010 Stelzl, Ulrich
    Systematic protein interaction studies are an important part of functional genomics research. A powerful method to decipher protein-protein interaction networks is the yeast two-hybrid system that allows studying the possible interaction of billions of protein pairs. Resulting interactions are represented in protein networks which provide a framework for a systems understanding of the molecular biology of the cell and contribute to medical practice, facilitating identification of human disease genes and an improved interpretation of patient samples and records.
  • Structure and Function of Membrane Proteins

    2010 Kühlbrandt, Werner
    The research of the Department of Structural Biology focuses on understanding the structural basis of membrane transport and biological energy conversion at the highest possible level of detail. The main methods are crystallography of membrane protein crystals (2D and 3D), single-particle cryo-EM and electron cryo-tomography (cryo-ET) of biological membranes. With few exceptions, all membrane proteins for crystallography, as well as membranes or organelles for tomography are produced within the group.


  • Computational modelling of biological processes

    2009 Wierling, Christoph; Herwig, Ralf
    The development of computational models for biological processes opens the possibility to predict new effects of virtual targeted perturbations that can in turn be validated by experimental observations. Such predictions are highly relevant for many practical applications, for example the development of new drugs. Through the last years, the Bioinformatics group has been developing different tools, methods, and databases that support the computational modeling of biological processes, such as the pathway integration database ConsensusPathDB and the modeling system PyBioS.
  • The interconnection of mutagenic and cellular processes during the evolution of mammals

    2009 Arndt, Peter F.
    The huge amount of DNA sequence data derived from a multitude of species, which is at our disposal today, allows comparative studies of genome evolution. Such studies afford to trace back the evolution of genomic DNA sequences and to single out and study the processes that play an important role in changing and shaping the genomes of mammals. The interaction of these processes with other cellular operations is now being investigated and better understood.
  • Light-driven channels and ion pumps as tools for neuroscience

    2009 Bamberg, Ernst
    Remote control of neural cells by light by means of the light-gated cation channel Channelrhodopsin2 (ChR2) and of the light-driven Cl- pump Halorhodopsin (NphR) fulfils a long lasting desire of neurobiologists. With this method neurons in culture as well as in the brain of living animals can be activated or inactivated at different wavelengths of the exciting light in a non invasive, electrode free manner with high temporal and even more important with an up to now unknown spatial resolution. This new technique has set the basis for the fast developing field of optogenetics.


  • Interaction networks in protein structures

    2008 Lappe, Michael
    The central topic of the Bioinformatics / Structural Proteomics group is the analysis and prediction of protein structures via networks. Methods are developed to reconstruct the 3D structure from such networks with the aim to identify the determining contacts in these structure networks. This interdisciplinary work provides potential application in protein and drug design.
  • Regulatory networks of trunk formation in mammals

    2008 Herrmann, Bernhard G.
    Mesoderm formation is an important process of embryonic development. It plays an essential role in trunk formation and organ development in mammals. It is controlled by several interacting signalling pathways, which also play an important role in tumour progression. Novel methods are utilized for deciphering the complex regulatory networks comprising thousands of gene products, which control mesoderm formation in the embryo and in tumours.
  • Molecular Neurogenetics of the Mouse Olfactory System

    2008 Spors, Hartwig; Mombaerts, Peter
    In the mouse, the sense of smell (olfaction) is mediated by more than 1200 odorant receptors (ORs), the largest gene family in the genome. These ORs are G-protein coupled receptors. Every olfactory sensory neuron (OSN) in the main olfactory epithelium is thought to express just one OR gene, from one allele. Axons of OSNs that express the same OR coalesce into the same structures in the olfactory bulb, termed glomeruli, where they form synapses with second-order neurons in the olfactory pathway.


  • Mathematical models demonstrate the integration of information through cellular signal transduction pathways

    2007 Klipp, Edda
    Molecular approaches reveal components and mechanisms of cellular stress sensing and adaptation. In addition, mathematical modeling has proven to foster the understanding of some basic principles of signal transduction and signal processing as well as of sensitivity and robustness of information perception and cellular response. Main modeling principles are exemplified here for a model organism, the yeast Saccharomyces cerevisiae.
  • Newly recognized functions of monoaminergic hormones: protein monoaminylation

    2007 Walther, Diego J.
    After the finalization of the human genome project, investigations into the transcriptome, proteome, and metabolome have been largely increased, since their concurrence determines the functionality of genes. In this context, recent mechanistic discoveries have induced a kind of “paradigm shift” regarding the mode of action of hormones and widened our understanding of these compounds in cell and gene regulation, particularly when involved in human diseases.
  • Electrogenic and electroneutral catalysis by dihaem-containing succinate:quinone oxidoreductases

    2007 Lancaster, C. Roy D.
    The atomic structures of a bacterial succinate:quinone oxidoreductase and of mechanistically interesting variants have been determined by X-ray crystallography. Together with complementary functional studies, these results have yielded unequivocal evidence for a novel type of essential transmembrane proton transfer driving transmembrane electron transfer in this protein complex.
  • Structure and Molecular Mechanism of the Sodium-Proton-Antiporter NhaA and the Cytochrome-bc1-Complex

    2007 Hunte, Carola
    1. Variants of the mitochondrial cytochrome bc1 complex created by site-directed mutagenesis produce deleterious oxygen radicals, which are implied in aging processes and pathophysiological conditions. 2. The regulation of the cellular ion composition by sodium-proton-antiporters is essential. The first atomic structure of such a transporter was determined and a mechanistic model for regulation and transport developed.


  • Molecular mechanisms of skeletal development

    2006 Mundlos, Stefan
    The research group Development & Disease focuses on the molecular basis by which form and structure of the skeleton are regulated during vertebrate development. Our approach combines research on human genetic disorders with gene function analysis in vitro and in animal models. The studies are carried out in close collaboration with the Institute of Medical Genetics at the Charité, Berlin. Recent advances in the identification and functional analysis of human gene mutations have provided new insights into the biology and pathology of limb malformations and, in particular, in the mechanisms of joint formation. Genetic screens have identified a large number of novel genes that are currently investigated for their role in normal bone development, in disease, and during the regeneration of bone and cartilage.
  • Ribosomes, the cellular production plants of proteins, loose their secrets

    2006 Fucini, Paola; Nierhaus, Knud H.
    Ribosomes translate the genetic DNA information into the amino-acid sequence of proteins and are one of the most complicated structures of the cell. High resolution methods such as X-ray analysis and cryo-electron microscopy as well as improved functional methods have led to a quantum leap in our understanding of the mechanisms of the ribosome by deducing functionality from structure.
  • Mechanisms of membrane transport visualized by electron microscopy and x-ray crystallography

    2006 Kühlbrandt, Werner; Appel, Matthias; Barton, Bastian; Kalthoff, Christoph; Raunser, Stefan; Schröder, Rasmus; Vinothkumar, Kutti Ragunath; Yildiz, Özkan
    In recent research the Department of Structural Biology at the Max Planck Institute of Biophysics addressed membrane transport proteins from thermophilic archaea, which are more robust than their eukaryotic counterparts yet often quite similar to them, and thus serve as good models for medically relevant systems. They determined the structure of a signaling protein that regulates nitrogen uptake in archaea and bacteria in three different states, which helped them to elucidate the regulatory mechanism. Furthermore they investigated pH- and ion-induced conformational changes that accompany activation and ion transport in sodium-proton exchange proteins, and in the outer membrane porin OmpG from E. coli.


  • Analysis of binding sites for the activation of genes

    2005 Vingron, Martin
    Transcription factors play a central role for the regulation of genes. The Department of Computational Biology at the MPI for Molecular Genetics utilizes a panel of mathematical methods to analyze function and interaction of transcription factors in order to achieve new insights into gene regulation.
  • From genetic information to the treatment of diseases

    2005 Lehrach, Hans
    Thanks to the sequencing of the human genome, we have access to detailed and extensive information about the complexity of biological processes. The comparison of the human genome with the chimpanzee genome leeds to a better understanding of molecular processes. This will set up a basis for the advancement of new medical diagnostics and treatments.
  • Channelrhodopsin-1 and -2: function and application of a new class of ion channels

    2005 Nagel, Georg; Bamberg, Ernst
    Phototaxis and photophobic responses of the green alga Chlamydomonas reinhardtii are mediated by microbial rhodopsins with the chromophore retinal. Sequence comparison with other microbial rhodopsins from archaea as the light-driven proton pump bacteriorhodopsin and the light-driven chloride pump halorhodopsin showed an overall homology of 15 to 20 % of those two algae chromoproteins. It is equally important that the N-terminal half approximately 300 of 712 and 737 amino acids, respectively, comprises seven hypothetical transmembrane helices as it is typical for rhodopsin-like proteins. Morover, several of the amino acids are conserved, which define the retinal binding site as well as the H+ -transporting pathway in bacteriorhodopsin. Recently, we demonstrated that two of these retinal-binding proteins from the eyespot of the alga, which we named channelrhodopsin-1 and -2 (ChR1 and ChR2), showed channel activity, directly activated by light when expressed in oocytes from Xenopus laevis or HEK 293 cells. ChR1 is selective for protons, whereas ChR2 is also conductive for monovalent and divalent cations. For both proteins the N-terminal hydrophobic half is sufficient to enable light-gated channel activity, demonstrating that the seven transmembrane helix motif represents a new class of ion channels.


  • Molecular basis of hereditary cognitive disorders

    2004 Ropers, Hans-Hilger
    Mental retardation is the biggest unsolved problem of Medical Genetics and a major burden for Health Care. Most severe forms of mental retardation are due to chromosome aberrations and gene defects, but so far, only a small proportion of these defects is known. For the mapping and identification of the relevant genetic factors we employ four different complementary strategies: i. investigation of patients with balanced chromosome rearrangements; ii. development and application of methods for high-resolution detection of unbalanced changes in the DNA; iii. systematic search for mutations in families with X-linked mental retardation; and iv. mapping of autosomal recessive gene defects by identifying homozygous genome segments in children of consanguineous parents. During recent years we have already identified numerous molecular causes of cognitive disorders. The characterization of these genes promises major progress for the diagnosis and prevention of mental retardation as well as new insights into normal and disturbed brain development and function.
  • Regulatory networks during embryogenesis of vertebrates

    2004 Herrmann, Bernhard G.
    The development of the body anlage with its organs is controlled by a multitude of complex regulatory mechanisms which follow a strict order. On top of these processes is the formation of mesenchyme, an event with similarities to metastasis formation of tumors. Novel methods are utilized to unravel regulatory networks controlling mesenchyme formation and tissue differentiation.
  • The One-Carbon Carrier Tetrahydromethanopterin in Enzymes

    2004 Ermler, Ulrich; Acharya, Pryamvada
    The one-carbon (C1) carrier tetrahydromethanopterin (H4MPT), that non-covalently binds as cofactor to proteins, became more and more important in the last years, as it was discovered in several phylogenetically distinct microorganisms where it plays a pronounced role in the C1 metabolism. Interestingly, its structure is highly similar to that of tetrahydrofolate (H4F), the most universal C1 carrier in biochemistry, but most likely H4MPT and H4F were separately developed within a convergent evolutionary process. The mode how H4MPT binds to enzymes was recently established on a structural level for two systems that will be introduced.


  • Structure and molecular mechanisms of membrane transport proteins

    2003 Collinson, Ian; Kühlbrandt, Werner; Model, Kirstin; Parcej, David; Standfuss, Jörg; Terwisscha van Scheltinga, Anke; Ziegler, Christine
    The Department of Structural Biology at the Max Planck Institute of Biophysics focuses on the structure and molecular mechanisms of membrane transport proteins. The structures of membrane proteins purified from natural sources or expressed in suitable host organisms are determined by electron microscopy or x-ray crystallography. The 2.5Å x-ray structure of the plant light-harvesting complex LHC-II reveals the mechanism of photoprotection and a likely pathway for dissipating excess solar energy. A three-dimensional map of a neuronal ion channel, determined by single-particle electron microscopy, shows the position of the alpha and beta subunits in the functional assembly. The 8Å map of the bacterial protein translocase SecYEG in the membrane shows how the structure adapts to the early steps of protein translocation. Structural studies of the protein translocase from outer and inner membranes of mitochondria reveal a twin pore. Two-dimensional crystals of various secondary transporters show different arrangements of membrane-spanning helices, indicative of different transport mechanisms.
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