10.7 Concluding Remarks
Analysis of the structure and dynamics of big macromolecular complexes is one of the great challenges of the postgenomic era. It is expected that in the next few years a great number of protein domain structures will be made available through X-ray crystallography and NMR studies, as all branches of biology strive to process the avalanche of data coming from genome sequencing. The understanding of cellular functions requires studying these domains in their context, taking part in the big macromolecular complexes and within the framework of living cells. The contributions from cryo-EM and cryo-ET can bring us to a new scenario, where the researcher could “see” individual molecular motors working within an astonishing complicated factory, the cell. We are convinced that all the possibilities that 3DEM offers will illustrate these and many other breakthroughs in a not very distant future.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Abrescia NG, Cockburn JJ, Grimes JM, Sutton GC, Diprose JM, Butcher SJ, Fuller SD, San Martín, C, Burnett RM, Stuart DI, Bamford DH, Bamford JK. (2004) Insights into assembly from structural analysis of bacteriophage PRD1. Nature 432:68–74
Baumeister W, Steven AC (2000) Macromolecular electron microscopy in the era of structural genomics. Trends Biochem Sci 25:624–631
Böttcher B, Wynne SA, Crowther RA (1997) Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy. Nature 386:88–91
Conway JF, Cheng N, Zlotnick A, Wingfield PT, Stahl SJ, Steven AC (1997) Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy. Nature 386:91–94
DeRosier DJ, Klug A (1968) Reconstruction of three-dimensional structures from electron micrographs. Nature 217:130–134
Dubochet J, Adrian M, Chang JJ, Homo JC, Lepault J, McDowall AW, Schultz P (1988) Cryo-electron microscopy of vitrified specimens. Q Rev Biophys 21:129–228
Frangakis AS, Bohm J, Forster F, Nickell S, Nicastro D, Typke D, Hegerl R, Baumeister W (2002) Identification of macromolecular complexes in cryoelectron tomograms of phantom cells. Proc Natl Acad Sci USA 99:14153–14158
Frey TG, Mannella CA (2000) The internal structure of mitochondria. Trends Biochem Sci 25:319–324
Gao H, Sengupta J, Valle M, Korostelev A, Eswar N, Stagg SM, van Roey P, Agrawal RK, Harvey SC, Sali A, Chapman MS, Frank J (2003) Study of the structural dynamics of the E coli 70S ribosome using real-space refinement. Cell 113:789–801
Gao H, Valle M, Ehrenberg M, Frank J (2004) Dynamics of EF-G interaction with the ribosome explored by classification of a heterogeneous cryo-EM dataset. J Struct Biol 147:283–290
Grimes JM, Jakana J, Ghosh M, Basak AK, Roy P, Chiu W, Stuart DI, Prasad BV (1997) An atomic model of the outer layer of the bluetongue virus core derived from X-ray crystallography and electron cryomicroscopy. Structure 5:885–893
Grimes JM, Burroughs JN, Gouet, P, Diprose JM, Malby R, Ziéntara S, Mertens PPC, Stuart DI. (1998) The atomic structure of the bluetongue virus core. Nature 395:470–478
Henderson R (2004) Realizing the potential of electron cryo-microscopy. Q Rev Biophys 37:3–13
Henderson R, Baldwin JM, Ceska TA, Zemlin F, Beckmann E, Downing KH (1990) Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J Mol Biol 213:899–929
Heymann JB, Cheng, N, Newcomb WW, Trus BL, Brown JC, Steven AC (2003) Dynamics of herpes simplex virus capsid maturation visualized by time-lapse cryo-electron microscopy. Nat Struct Biol 10:334–341
Kimura Y, Vassylyev DG, Miyazawa A, Kidera A, Matsushima M, Mitsuoka K, Murata K, Hirai T, Fujiyoshi Y (1997) Surface of bacteriorhodopsin revealed by high-resolution electron crystallography. Nature 389:206–211
Kostyuchenko VA, Leiman PG, Chipman PR, Kanamaru, S, van Raaij MJ, Arisaka, F, Mesyanzhinov VV, Rossmann MG (2003) Three-dimensional structure of bacteriophage T4 baseplate. Nat Struct Biol 10:688–693
Kühlbrandt W, Wang DN, Fujiyoshi Y (1994) Atomic model of plant light-harvesting complex by electron crystallography. Nature 367:614–621
Kuhn RJ, Zhang, W, Rossmann MG, Pletnev SV, Corver, J, Lenches, E, Jones CT, Mukhopadhyay, S, Chipman PR, Strauss EG, Baker TS, Strauss JH (2002) Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108:717–725
Ludtke SJ, Chen DH, Song JL, Chuang DT, Chiu W (2004) Seeing GroEL at 6 Å resolution by single particle electron cryomicroscopy. Structure 12:1129–1136
Medalia O, Weber I, Frangakis AS, Nicastro D, Gerisch G, Baumeister W (2002) Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography. Science 298:1209–1213
Miyazawa A, Fujiyoshi Y, Unwin N (2003) Structure and gating mechanism of the acetylcholine receptor pore. Nature 424:949–955
Mukhopadhyay S, Kim BS, Chipman PR, Rossmann MG, Kuhn RJ (2003) Structure of west nile virus. Science 302:248
Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (2000) Structural determinants of water permeation through aquaporin-1. Nature 407:599–605
Nogales E, Wolf SG, Downing KH (1998) Structure of the alpha beta tubulin dimer by electron crystallography. Nature 391:199–203
Nogales E, Whittaker M, Milligan RA, Downing KH (1999) High-resolution model of the microtubule. Cell 96:79–88
Radon J (1917) Über die Bestimmung von Funktionen durch ihre integralwerte längs gewisser Mannigfaltigkeiten (on the determination of functions from their integrals along certain manifolds). Ber Verh Saechs Akad Wiss Leipzig Math-Phys Kl 69:262–277
San Martín C, Burnett RM, de Haas F, Heinkel R, Rutten T, Fuller SD, Butcher SJ, Bamford DH (2001) Combined EM/X-ray imaging yields a quasi-atomic model of the adenovirus-related bacteriophage PRD1 and shows key capsid and membrane interactions. Structure 9:917–930
Schoehn G, Quaite-Randall E, Jimenez JL, Joachimiak A, Saibil HR (2000) Three conformations of an archaeal chaperonin, TF55 from Sulfolobus shibatae. J Mol Biol 296:813–819
Stark H, Dube P, Luhrmann R, Kastner B (2001) Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. Nature 409:539–542
Steinmetz MO, Hoenger A, Tittmann P, Fuchs KH, Gross H, Aebi U (1998) An atomic model of crystalline actin tubes: combining electron microscopy with X-ray crystallography. J Mol Biol 278:703–711
Subramaniam S, Henderson R (1999) Electron crystallography of bacteriorhodopsin with millisecond time resolution. J Struct Biol 128:19–25
Valle M, Zavialov A, Li W, Stagg SM, Sengupta J, Nielsen RC, Nissen P, Harvey SC, Ehrenberg M, Frank J (2003a) Incorporation of aminoacyl-tRNA into the ribosome as seen by cryo-electron microscopy. Nat Struct Biol 10:899–906
Valle M, Zavialov A, Sengupta J, Rawat U, Ehrenberg M, Frank J (2003b) Locking and unlocking of ribosomal motions. Cell 114:123–134
Yonekura K, Maki-Yonekura S, Namba K (2003) Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature 424:643–650
Zhang W, Chipman PR, Corver J, Johnson PR, Zhang Y, Mukhopadhyay S, Baker TS, Strauss JH, Rossmann MG, Kuhn RJ (2003) Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol 10:907–912
Zhou ZH, Dougherty M, Jakana J, He J, Rixon FJ, Chiu W (2000) Seeing the herpesvirus capsid at 8.5 Å. Science 288:877–880
Zhou ZH, Zhang H, Jakana J, Lu XY, Zhang JQ (2003) Cytoplasmic polyhedrosis virus structure at 8 Å by electron cryomicroscopy: structural basis of capsid stability and mRNA processing regulation. Structure 11:651–663
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
San Martín, C., Valle, M.K. (2006). Three-Dimensional Electron Microscopy. The Coming of Age of a Versatile Structural Biology Technique. In: Arrondo, J.L.R., Alonso, A. (eds) Advanced Techniques in Biophysics. Springer Series in Biophysics, vol 10. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-30786-9_10
Download citation
DOI: https://doi.org/10.1007/3-540-30786-9_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-30700-6
Online ISBN: 978-3-540-30786-0
eBook Packages: Physics and AstronomyPhysics and Astronomy (R0)