Single-Particle Reconstruction of Biological Molecules-Story in a Sample (Nobel Lecture).

Pictures tell a thousand words: The development of single-particle cryo-electron microscopy set the stage for high-resolution structure determination of biological molecules. In his Nobel lecture, J. Frank describes the ground-breaking discoveries that have enabled the development of cryo-EM. The method has taken biochemistry into a new era.

[1]  J. Takagi,et al.  Advances in domain and subunit localization technology for electron microscopy , 2019, Biophysical Reviews.

[2]  Dmitry Lyumkis,et al.  Challenges and opportunities in cryo-EM single-particle analysis , 2019, The Journal of Biological Chemistry.

[3]  Hiro Furukawa,et al.  Dissecting diverse functions of NMDA receptors by structural biology. , 2019, Current opinion in structural biology.

[4]  S. Burley,et al.  Outlier analyses of the Protein Data Bank archive using a probability-density-ranking approach , 2018, Scientific Data.

[5]  J. Frank.  The Envelope of Electron Microscopic Transfer Functions for Partially Coherent Illumination , 2018 .

[6]  J. Frank,et al.  Conformational Dynamics and Energy Landscapes of Ligand Binding in RyR1 , 2017, bioRxiv.

[7]  E. C. Twomey,et al.  Channel opening and gating mechanism in AMPA-subtype glutamate receptors , 2017, Nature.

[8]  Nikolaus Grigorieff,et al.  Ensemble cryo-EM elucidates the mechanism of translation fidelity , 2017, Nature.

[9]  E. C. Twomey,et al.  Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes , 2017, Neuron.

[10]  K. Holmes.  Aaron Klug - A Long Way from Durban: A Biography , 2017 .

[11]  Joachim Frank,et al.  Advances in the field of single-particle cryo-electron microscopy over the last decade , 2017, Nature Protocols.

[12]  Joachim Frank,et al.  Key Intermediates in Ribosome Recycling Visualized by Time-Resolved Cryoelectron Microscopy. , 2016, Structure.

[13]  W. Baumeister,et al.  Cryo-EM structure of haemoglobin at 3.2 Å determined with the Volta phase plate , 2016, Nature Communications.

[14]  J. Frank,et al.  Structure and assembly model for the Trypanosoma cruzi 60S ribosomal subunit , 2016, Proceedings of the National Academy of Sciences.

[15]  J. Frank,et al.  Structural Basis for Gating and Activation of RyR1 , 2016, Cell.

[16]  David J Weber,et al.  Structure of the STRA6 receptor for retinol uptake , 2016, Science.

[17]  E. C. Twomey,et al.  Elucidation of AMPA receptor–stargazin complexes by cryo–electron microscopy , 2016, Science.

[18]  Joachim Frank,et al.  Continuous changes in structure mapped by manifold embedding of single-particle data in cryo-EM. , 2016, Methods.

[19]  Joachim Frank,et al.  Two promising future developments of cryo-EM: capturing short-lived states and mapping a continuum of states of a macromolecule. , 2016, Microscopy.

[20]  E. Nogales.  The development of cryo-EM into a mainstream structural biology technique , 2015, Nature Methods.

[21]  Joachim Frank,et al.  Dynamical features of the Plasmodium falciparum ribosome during translation , 2015, Nucleic acids research.

[22]  Toh-Ming Lu,et al.  Structural dynamics of ribosome subunit association studied by mixing-spraying time-resolved cryogenic electron microscopy. , 2015, Structure.

[23]  J. Frank,et al.  Activation of GTP hydrolysis in mRNA-tRNA translocation by elongation factor G , 2015, Science Advances.

[24]  Hstau Y Liao,et al.  Trajectories of the ribosome as a Brownian nanomachine , 2014, Proceedings of the National Academy of Sciences.

[25]  J. Frank,et al.  Structure of a mammalian ryanodine receptor , 2014, Nature.

[26]  T. Mielke,et al.  Regulation of the Mammalian Elongation Cycle by Subunit Rolling: A Eukaryotic-Specific Ribosome Rearrangement , 2014, Cell.

[27]  R. Agrawal,et al.  Initial bridges between two ribosomal subunits are formed within 9.4 milliseconds, as studied by time-resolved cryo-EM , 2014, Proceedings of the National Academy of Sciences.

[28]  J. Frank,et al.  Structure of the Mammalian Ribosomal 43S Preinitiation Complex Bound to the Scanning Factor DHX29 , 2013, Cell.

[29]  J. Frank,et al.  High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome , 2013, Nature.

[30]  Klaus Schulten,et al.  Structural characterization of mRNA-tRNA translocation intermediates , 2012, Proceedings of the National Academy of Sciences.

[31]  Sjors H.W. Scheres,et al.  A Bayesian View on Cryo-EM Structure Determination , 2012, 2012 9th IEEE International Symposium on Biomedical Imaging (ISBI).

[32]  J. Frank.  Molecular Machines in Biology: Visualization of Molecular Machines by Cryo-Electron Microscopy , 2011 .

[33]  T. Steitz.  From the structure and function of the ribosome to new antibiotics , 2011 .

[34]  Joachim Frank,et al.  Structure and dynamics of a processive Brownian motor: the translating ribosome. , 2010, Annual review of biochemistry.

[35]  Toh-Ming Lu,et al.  Monolithic microfluidic mixing-spraying devices for time-resolved cryo-electron microscopy. , 2009, Journal of structural biology.

[36]  V. Ramakrishnan,et al.  What recent ribosome structures have revealed about the mechanism of translation , 2009, Nature.

[37]  Klaus Schulten,et al.  Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis , 2009, Proceedings of the National Academy of Sciences.

[38]  Jianlin Lei,et al.  Recognition of aminoacyl-tRNA: a common molecular mechanism revealed by cryo-EM , 2008, The EMBO journal.

[39]  Joachim Frank,et al.  Exploration of parameters in cryo-EM leading to an improved density map of the E. coli ribosome. , 2008, Journal of structural biology.

[40]  Leonardo G. Trabuco,et al.  Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics. , 2008, Structure.

[41]  K. Mossman.  Profile of Joachim Frank , 2007, Proceedings of the National Academy of Sciences.

[42]  J. Frank.  Three-Dimensional Electron Microscopy of Macromolecular Assemblies , 2006 .

[43]  Joachim Frank,et al.  Molding atomic structures into intermediate-resolution cryo-EM density maps of ribosomal complexes using real-space refinement. , 2005, Structure.

[44]  Scott M Stagg,et al.  Incorporation of aminoacyl-tRNA into the ribosome as seen by cryo-electron microscopy , 2003, Nature Structural Biology.

[45]  J. Frank,et al.  Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Joachim Frank,et al.  Locking and Unlocking of Ribosomal Motions , 2003, Cell.

[47]  M. S. Chapman,et al.  Study of the Structural Dynamics of the E. coli 70S Ribosome Using Real-Space Refinement , 2003, Cell.

[48]  J. Frank,et al.  A twisted tRNA intermediate sets the threshold for decoding. , 2003, RNA.

[49]  Joachim Frank,et al.  Cryo‐EM reveals an active role for aminoacyl‐tRNA in the accommodation process , 2002, The EMBO journal.

[50]  J Frank,et al.  Hepatitis C Virus IRES RNA-Induced Changes in the Conformation of the 40S Ribosomal Subunit , 2001, Science.

[51]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[52]  Joachim Frank,et al.  A ratchet-like inter-subunit reorganization of the ribosome during translocation , 2000, Nature.

[53]  Joachim Frank,et al.  EF-G-dependent GTP hydrolysis induces translocation accompanied by large conformational changes in the 70S ribosome , 1999, Nature Structural Biology.

[54]  J. Frank.  How the Ribosome Works , 1998, American Scientist.

[55]  Joachim Frank,et al.  A 9 Å Resolution X-Ray Crystallographic Map of the Large Ribosomal Subunit , 1998, Cell.

[56]  J Frank,et al.  Visualization of elongation factor G on the Escherichia coli 70S ribosome: the mechanism of translocation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[57]  J. Frank,et al.  Three-dimensional reconstruction with contrast transfer function correction from energy-filtered cryoelectron micrographs: procedure and application to the 70S Escherichia coli ribosome. , 1997, Journal of structural biology.

[58]  J. Frank,et al.  A common-lines based method for determining orientations for N > 3 particle projections simultaneously. , 1996, Ultramicroscopy.

[59]  J. Frank,et al.  A model of protein synthesis based on cryo-electron microscopy of the E. coli ribosome , 1995, Nature.

[60]  R. Henderson.  The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules , 1995, Quarterly Reviews of Biophysics.

[61]  N. Unwin,et al.  Analysis of transient structures by cryo-microscopy combined with rapid mixing of spray droplets. , 1994, Ultramicroscopy.

[62]  J Frank,et al.  Cryo-electron microscopy and three-dimensional reconstruction of the calcium release channel/ryanodine receptor from skeletal muscle , 1994, The Journal of cell biology.

[63]  J. Frank,et al.  Quaternary structure of Octopus vulgaris hemocyanin. Three-dimensional reconstruction from frozen-hydrated specimens and intramolecular location of functional units Ove and Ovb. , 1994, Journal of molecular biology.

[64]  J. Frank,et al.  The ribosome at improved resolution: new techniques for merging and orientation refinement in 3D cryo-electron microscopy of biological particles. , 1994, Ultramicroscopy.

[65]  J. Frank,et al.  Cryo-EM of the native structure of the calcium release channel/ryanodine receptor from sarcoplasmic reticulum. , 1992, Biophysical journal.

[66]  J. Frank,et al.  Three-dimensional reconstruction of the 70S Escherichia coli ribosome in ice: the distribution of ribosomal RNA , 1991, The Journal of cell biology.

[67]  J. Frank,et al.  Three‐dimensional reconstruction from a single‐exposure, random conical tilt series applied to the 50S ribosomal subunit of Escherichia coli , 1987, Journal of microscopy.

[68]  J. Frank,et al.  Three‐dimensional structure of the large ribosomal subunit from Escherichia coli. , 1987, The EMBO journal.

[69]  J Frank,et al.  A NEW 3‐D RECONSTRUCTION SCHEME APPLIED TO THE 50S RIBOSOMAL SUBUNIT OF E. COLI , 1986, Journal of microscopy.

[70]  J. Frank,et al.  Representation of three‐dimensionally reconstructed objects in electron microscopy by surfaces of equal density , 1984, Journal of microscopy.

[71]  J. Dubochet,et al.  Cryo-electron microscopy of viruses , 1984, Nature.

[72]  W. O. Saxton,et al.  The correlation averaging of a regularly arranged bacterial cell envelope protein , 1982, Journal of microscopy.

[73]  J Frank,et al.  Computer averaging of electron micrographs of 40S ribosomal subunits. , 1981, Science.

[74]  J. Dubochet,et al.  VITRIFICATION OF PURE WATER FOR ELECTRON MICROSCOPY , 1981 .

[75]  J Frank,et al.  Structural details of membrane-bound acetylcholine receptor from Tropedo marmorata. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[76]  R. Henderson,et al.  Three-dimensional model of purple membrane obtained by electron microscopy , 1975, Nature.

[77]  J. Frank,et al.  Signal-to-noise ratio of electron micrographs obtained by cross correlation , 1975, Nature.

[78]  R. Glaeser,et al.  Electron Diffraction of Frozen, Hydrated Protein Crystals , 1974, Science.

[79]  W Hoppe,et al.  Three-dimensional reconstruction of individual negatively stained yeast fatty-acid synthetase molecules from tilt series in the electron microscope. , 1974, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[80]  M. Beer,et al.  The possibilities and prospects of obtaining high-resolution information (below 30 Å) on biological material using the electron microscope , 1974, Quarterly Reviews of Biophysics.

[81]  J Frank,et al.  A study of heavy-light atom discrimination in bright-field electron microscopy using the computer. , 1972, Biophysical journal.

[82]  R. Glaeser,et al.  Limitations to significant information in biological electron microscopy as a result of radiation damage. , 1971, Journal of ultrastructure research.

[83]  R. Crowther,et al.  Procedures for three-dimensional reconstruction of spherical viruses by Fourier synthesis from electron micrographs. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[84]  W. Hoppe,et al.  Anwendung des Bilddifferenzverfahrens auf die Untersuchung von Strukturänderungen dünner Kohlefolien bei Elektronenbestrahlung , 1970, Berichte der Bunsengesellschaft für physikalische Chemie.

[85]  W. Hoppe,et al.  Einige Erfahrungen mit der rechnerischen Analyse und Synthese von elektronenmikroskopischen Bildern hoher Auflösung , 1970, Berichte der Bunsengesellschaft für physikalische Chemie.

[86]  A. Klug,et al.  Three Dimensional Reconstructions of Spherical Viruses by Fourier Synthesis from Electron Micrographs , 1970, Nature.

[87]  D. J. De Rosier,et al.  Reconstruction of Three Dimensional Structures from Electron Micrographs , 1968, Nature.

[88]  F. Thon.  Notizen: Zur Defokussierungsabhängigkeit des Phasenkontrastes bei der elektronenmikroskopischen Abbildung , 1966 .

[89]  G. Herman,et al.  Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization , 2007, Nature Methods.

[90]  F. Sigworth.  From cryo-EM, multiple protein structures in one shot , 2007, Nature Methods.

[91]  F. Sigworth.  A maximum-likelihood approach to single-particle image refinement. , 1998, Journal of structural biology.

[92]  Holger Stark,et al.  ANGULAR RECONSTITUTION IN THREE-DIMENSIONAL ELECTRON MICROSCOPY: HISTORICAL AND THEORETICAL ASPECTS , 1997 .

[93]  Joachim Frank,et al.  THREE DIMENSIONAL RECONSTRUCTION WITH CONTRAST TRANSFER COMPENSATION FROM DEFOCUS SERIES , 1997 .

[94]  J Frank,et al.  Three-dimensional reconstruction of single particles embedded in ice. , 1992, Ultramicroscopy.

[95]  M. van Heel.  Angular reconstitution: a posteriori assignment of projection directions for 3D reconstruction. , 1987, Ultramicroscopy.

[96]  M. Heel,et al.  Angular reconstitution: a posteriori assignment of projection directions for 3D reconstruction. , 1987 .

[97]  M. Heel,et al.  Exact filters for general geometry three dimensional reconstruction , 1986 .

[98]  J. Frank,et al.  The role of multivariate image analysis in solving the architecture of the Limulus polyphemus hemocyanin molecule. , 1984, Ultramicroscopy.

[99]  Joachim Frank,et al.  SPIDER—A modular software system for electron image processing , 1981 .

[100]  Joachim Frank,et al.  Use of multivariate statistics in analysing the images of biological macromolecules , 1981 .

[101]  J. Frank,et al.  Averages of glutamine synthetase molecules as obtained with various skin and electron dose conditions. , 1980, Journal of supramolecular structure.

[102]  Joachim Frank,et al.  The Role of Correlation Techniques in Computer Image Processing , 1980 .

[103]  J Frank,et al.  Reconstruction of glutamine synthetase using computer averaging. , 1978, Ultramicroscopy.

[104]  R. Wade,et al.  Electron microscope transfer functions for partially coherent axial illumination and chromatic defocus spread , 1977 .

[105]  J Frank,et al.  Motif detection in quantum noise-limited electron micrographs by cross-correlation. , 1977, Ultramicroscopy.

[106]  W. Baumeister,et al.  Relevance of three-dimensional reconstructions of stain distributions for structural analysis of biomolecules. , 1975, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[107]  J Frank,et al.  Averaging of low exposure electron micrographs of non-periodic objects. , 1975, Ultramicroscopy.

[108]  J. Frank.  Untersuchungen von elektronenmikroskopischen Aufnahmen hoher Auflösung mit Bilddifferenz- und Rekonstruktionsverfahren , 1970 .

[109]  O. Scherzer.  The Theoretical Resolution Limit of the Electron Microscope , 1949 .