Towards atomic resolution structural determination by single-particle cryo-electron microscopy.

Recent advances in cryo-electron microscopy and single-particle reconstruction (collectively referred to as 'cryoEM') have made it possible to determine the three-dimensional (3D) structures of several macromolecular complexes at near-atomic resolution ( approximately 3.8-4.5A). These achievements were accomplished by overcoming the challenges in sample handling, instrumentation, image processing, and model building. At near-atomic resolution, many detailed structural features can be resolved, such as the turns and deep grooves of helices, strand separation in beta sheets, and densities for loops and bulky amino acid side chains. Such structural data of the cytoplasmic polyhedrosis virus (CPV), the Epsilon 15 bacteriophage and the GroEL complex have provided valuable constraints for atomic model building using integrative tools, thus significantly enhancing the value of the cryoEM structures. The CPV structure revealed a drastic conformational change from a helix to a beta hairpin associated with RNA packaging and replication, coupling of RNA processing and release, and the long sought-after polyhedrin-binding domain. These latest advances in single-particle cryoEM provide exciting opportunities for the 3D structural determination of viruses and macromolecular complexes that are either too large or too heterogeneous to be investigated by conventional X-ray crystallography or nuclear magnetic resonance (NMR) methods.

[1]  Kenneth H Downing,et al.  Dose tolerance at helium and nitrogen temperatures for whole cell electron tomography. , 2005, Journal of structural biology.

[2]  G. Jensen,et al.  Observations on the behavior of vitreous ice at ~82 and ~12K , 2006 .

[3]  Joanita Jakana,et al.  Cytoplasmic polyhedrosis virus structure at 8 A by electron cryomicroscopy: structural basis of capsid stability and mRNA processing regulation. , 2003, Structure.

[4]  R. Henderson,et al.  Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. , 2003, Journal of molecular biology.

[5]  H. Saibil,et al.  Allosteric signaling of ATP hydrolysis in GroEL–GroES complexes , 2006, Nature Structural &Molecular Biology.

[6]  Pawel A Penczek,et al.  Three-dimensional spectral signal-to-noise ratio for a class of reconstruction algorithms. , 2002, Journal of structural biology.

[7]  N. Grigorieff,et al.  Noise bias in the refinement of structures derived from single particles. , 2004, Ultramicroscopy.

[8]  W Chiu,et al.  EMAN: semiautomated software for high-resolution single-particle reconstructions. , 1999, Journal of structural biology.

[9]  S. Harrison,et al.  Near-atomic resolution using electron cryomicroscopy and single-particle reconstruction , 2008, Proceedings of the National Academy of Sciences.

[10]  M. Sherman,et al.  Reliability of phases retrieved from 400‐kV spot‐scan images of purple membranes acquired on a slow‐scan CCD camera , 1997, Journal of microscopy.

[11]  Jun Kobayashi,et al.  Molecular Characterization of Bombyx mori Cytoplasmic Polyhedrosis Virus Genome Segment 4 , 2001, Journal of Virology.

[12]  A. Horwich,et al.  Structure and function in GroEL-mediated protein folding. , 1998, Annual review of biochemistry.

[13]  Gabriel C Lander,et al.  Automated cryoEM data acquisition and analysis of 284742 particles of GroEL. , 2006, Journal of structural biology.

[14]  D. Stuart,et al.  The atomic structure of the bluetongue virus core , 1998, Nature.

[15]  W. Chiu,et al.  Seeing GroEL at 6 A resolution by single particle electron cryomicroscopy. , 2004, Structure.

[16]  Sriram Subramaniam,et al.  Automated image acquisition and processing using a new generation of 4K x 4K CCD cameras for cryo electron microscopic studies of macromolecular assemblies. , 2003, Journal of structural biology.

[17]  T. Baker,et al.  Reovirus polymerase λ3 localized by cryo-electron microscopy of virions at a resolution of 7.6 Å , 2003, Nature Structural Biology.

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

[19]  Satoshi Murakami,et al.  Crystal Structure of the DsbB-DsbA Complex Reveals a Mechanism of Disulfide Bond Generation , 2006, Cell.

[20]  Werner K¨hlbrandt,et al.  Three-dimensional structure of plant light-harvesting complex determined by electron crystallography , 1991, Nature.

[21]  Z. Zhou,et al.  Visualization of Protein-RNA Interactions in Cytoplasmic Polyhedrosis Virus , 1999, Journal of Virology.

[22]  Wah Chiu,et al.  Determination of icosahedral virus structures by electron cryomicroscopy at subnanometer resolution. , 2003, Advances in protein chemistry.

[23]  T. Baker,et al.  A model-based approach for determining orientations of biological macromolecules imaged by cryoelectron microscopy. , 1996, Journal of structural biology.

[24]  R. Holland Cheng,et al.  Direct Evidence for the Size and Conformational Variability of the Pyruvate Dehydrogenase Complex Revealed by Three-dimensional Electron Microscopy , 2001, The Journal of Biological Chemistry.

[25]  Clinton S Potter,et al.  ACE: automated CTF estimation. , 2005, Ultramicroscopy.

[26]  Y. Modis,et al.  Atomic model of the papillomavirus capsid , 2002, The EMBO journal.

[27]  S. Harrison,et al.  Structure of the reovirus core at 3.6 Å resolution , 2000, Nature.

[28]  Robert M Glaeser,et al.  Historical background: Why is it important to improve automated particle selection methods? , 2004, Journal of structural biology.

[29]  Matthew L. Baker,et al.  Electron cryomicroscopy and bioinformatics suggest protein fold models for rice dwarf virus , 2001, Nature Structural Biology.

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

[31]  J. Maniloff,et al.  Virus taxonomy : eighth report of the International Committee on Taxonomy of Viruses , 2005 .

[32]  S. Harrison,et al.  Molecular model for a complete clathrin lattice from electron cryomicroscopy , 2004, Nature.

[33]  W Chiu,et al.  Prospects for using an IVEM with a FEG for imaging macromolecules towards atomic resolution. , 1993, Ultramicroscopy.

[34]  Keiko Ikeda,et al.  The molecular organization of cypovirus polyhedra , 2007, Nature.

[35]  W. Chiu,et al.  Seeing the herpesvirus capsid at 8.5 A. , 2000, Science.

[36]  J. Frank,et al.  Solution Structure of the E. coli 70S Ribosome at 11.5 Å Resolution , 2000, Cell.

[37]  S. Harrison,et al.  Lipid–protein interactions in double-layered two-dimensional AQP0 crystals , 2005 .

[38]  Andreas Engel,et al.  Structural determinants of water permeation through aquaporin-1 , 2000, Nature.

[39]  Nikolaus Grigorieff,et al.  Ewald sphere correction for single-particle electron microscopy. , 2006, Ultramicroscopy.

[40]  Richard Henderson,et al.  Molecular mechanism of vectorial proton translocation by bacteriorhodopsin , 2000, Nature.

[41]  K. Mizuguchi,et al.  Comparison of spatial arrangements of secondary structural elements in proteins. , 1995, Protein engineering.

[42]  D. Stuart,et al.  The structure of a cypovirus and the functional organization of dsRNA viruses , 1999, Nature Structural Biology.

[43]  M. Baker,et al.  Identification of secondary structure elements in intermediate-resolution density maps. , 2007, Structure.

[44]  N. Grigorieff,et al.  A dose-rate effect in single-particle electron microscopy. , 2008, Journal of structural biology.

[45]  P L Stewart,et al.  Digitally collected cryo‐electron micrographs for single particle reconstruction , 2000, Microscopy research and technique.

[46]  N. Nomura,et al.  Immobilization of diverse foreign proteins in viral polyhedra and potential application for protein microarrays , 2006, Proteomics.

[47]  Edward H Egelman,et al.  Issues of resolution and polymorphism in single-particle reconstruction. , 2003, Journal of structural biology.

[48]  P. Adams,et al.  Conformational variability in the refined structure of the chaperonin GroEL at 2.8 Å resolution , 1995, Nature Structural Biology.

[49]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[50]  J. Patton.  Segmented double-stranded RNA viruses : structure and molecular biology , 2008 .

[51]  R. Glaeser.  Review: electron crystallography: present excitement, a nod to the past, anticipating the future. , 1999, Journal of structural biology.

[52]  P. Argos,et al.  Is Sindbis a simple picornavirus with an envelope? , 1987, The EMBO journal.

[53]  Dong-Hua Chen,et al.  De novo backbone trace of GroEL from single particle electron cryomicroscopy. , 2008, Structure.

[54]  Stewart Shuman,et al.  X-Ray Crystallography Reveals a Large Conformational Change during Guanyl Transfer by mRNA Capping Enzymes , 1997, Cell.

[55]  Anchi Cheng,et al.  Automated molecular microscopy: the new Leginon system. , 2005, Journal of structural biology.

[56]  Denis Fellmann,et al.  A relational database for cryoEM: experience at one year and 50 000 images. , 2002, Journal of structural biology.

[57]  R. Sun,et al.  Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy. , 2008, Journal of structural biology.

[58]  Z. Zhou,et al.  3.88 Å structure of cytoplasmic polyhedrosis virus by cryo-electron microscopy , 2008, Nature.

[59]  A. Kidera,et al.  The structure of bacteriorhodopsin at 3.0 A resolution based on electron crystallography: implication of the charge distribution. , 1999, Journal of molecular biology.

[60]  John E. Johnson,et al.  Topologically linked protein rings in the bacteriophage HK97 capsid. , 2000, Science.

[61]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[62]  P. Stewart,et al.  CryoEM structure at 9A resolution of an adenovirus vector targeted to hematopoietic cells. , 2005, Journal of molecular biology.

[63]  M. van Heel,et al.  Fourier shell correlation threshold criteria. , 2005, Journal of structural biology.

[64]  M. Estes,et al.  Three-dimensional visualization of mRNA release from actively transcribing rotavirus particles , 1997, Nature Structural Biology.

[65]  M. Borgnia,et al.  Visualization of alpha-helical features in a density map constructed using 9 molecular images of the 1.8 MDa icosahedral core of pyruvate dehydrogenase. , 2004, Journal of structural biology.

[66]  A. Roseman.  Particle finding in electron micrographs using a fast local correlation algorithm. , 2003, Ultramicroscopy.

[67]  P. Mooney.  Optimization of image collection for cellular electron microscopy. , 2007, Methods in cell biology.

[68]  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.

[69]  Qibin Yang,et al.  Symmetry-adapted spherical harmonics method for high-resolution 3D single-particle reconstructions. , 2008, Journal of structural biology.

[70]  W. Chiu,et al.  Averaging tens to hundreds of icosahedral particle images to resolve protein secondary structure elements using a Multi-Path Simulated Annealing optimization algorithm. , 2007, Journal of structural biology.

[71]  M. Unser,et al.  A new resolution criterion based on spectral signal-to-noise ratios. , 1987, Ultramicroscopy.

[72]  Kenneth H. Downing,et al.  Structure of the αβ tubulin dimer by electron crystallography , 1998, Nature.

[73]  N Go,et al.  Diversity of functions of proteins with internal symmetry in spatial arrangement of secondary structural elements , 1999, Protein science : a publication of the Protein Society.

[74]  B. Gowen,et al.  ATP-Bound States of GroEL Captured by Cryo-Electron Microscopy , 2001, Cell.

[75]  M F Schmid,et al.  Finding and using local symmetry in identifying lower domain movements in hexon subunits of the herpes simplex virus type 1 B capsid. , 2001, Journal of molecular biology.

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

[77]  Full contrast transfer function correction in 3D cryo-EM reconstruction , 2004, 2004 International Conference on Communications, Circuits and Systems (IEEE Cat. No.04EX914).

[78]  M. Baker,et al.  Coat protein fold and maturation transition of bacteriophage P22 seen at subnanometer resolutions , 2003, Nature Structural Biology.

[79]  F. Zemlin,et al.  Structure of keyhole limpet hemocyanin type 1 (KLH1) at 15 A resolution by electron cryomicroscopy and angular reconstitution. , 1997, Journal of molecular biology.

[80]  Nikolaus Grigorieff,et al.  FREALIGN: high-resolution refinement of single particle structures. , 2007, Journal of structural biology.

[81]  Holger Stark,et al.  Electron radiation damage to protein crystals of bacteriorhodopsin at different temperatures , 1996 .

[82]  Bjoern Sander,et al.  Molecular Architecture of the Multiprotein Splicing Factor SF3b , 2003, Science.

[83]  P. Wingfield,et al.  Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy , 1997, Nature.

[84]  D. DeRosier.  Correction of high-resolution data for curvature of the Ewald sphere. , 2000, Ultramicroscopy.

[85]  B. Böttcher,et al.  Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy , 1997, Nature.

[86]  Matthew L. Baker,et al.  Backbone structure of the infectious ε15 virus capsid revealed by electron cryomicroscopy , 2008, Nature.

[87]  N. Grigorieff,et al.  Ab initio resolution measurement for single particle structures. , 2007, Journal of structural biology.

[88]  Yuyao Liang,et al.  IMIRS: a high-resolution 3D reconstruction package integrated with a relational image database. , 2002, Journal of structural biology.

[89]  H. Stark,et al.  Advantages of CCD detectors for de novo three-dimensional structure determination in single-particle electron microscopy. , 2005, Journal of structural biology.

[90]  Wolfgang Baumeister,et al.  Electron tomography: towards visualizing the molecular organization of the cytoplasm. , 2002, Current opinion in structural biology.

[91]  Tamir Gonen,et al.  Aquaporin-0 membrane junctions reveal the structure of a closed water pore , 2004, Nature.

[92]  Z. Zhou,et al.  Structural Comparisons of Empty and Full Cytoplasmic Polyhedrosis Virus , 2003, The Journal of Biological Chemistry.

[93]  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.

[94]  A. R. Faruqi,et al.  CCD detectors in high-resolution biological electron microscopy , 2000, Quarterly Reviews of Biophysics.

[95]  Matthew L. Baker,et al.  A 9 Å single particle reconstruction from CCD captured images on a 200 kV electron cryomicroscope , 2004 .

[96]  G. Kleywegt,et al.  Detecting folding motifs and similarities in protein structures. , 1997, Methods in enzymology.

[97]  G. Jensen,et al.  Defocus-gradient corrected back-projection. , 2000, Ultramicroscopy.

[98]  J Jakana,et al.  Protein subunit structures in the herpes simplex virus A-capsid determined from 400 kV spot-scan electron cryomicroscopy. , 1994, Journal of molecular biology.

[99]  M van Heel,et al.  The Escherichia coli large ribosomal subunit at 7.5 A resolution. , 1999, Structure.

[100]  W Chiu,et al.  CTF determination of images of ice-embedded single particles using a graphics interface. , 1996, Journal of structural biology.

[101]  Grant J Jensen,et al.  A comparison of liquid nitrogen and liquid helium as cryogens for electron cryotomography. , 2006, Journal of structural biology.

[102]  Kevin Cowtan,et al.  research papers Acta Crystallographica Section D Biological , 2005 .