Faculty Guide

Title

W. M. Keck Professor of Biochemistry and Howard Hughes Medical Institute Investigator

Biochemistry
Rosenstiel Basic Medical Sciences Research Center

Expertise

High resolution electron cryo-microscopy of membrane proteins and channels.

Awards and Honors

NIH program project grant "Structure-Function Analysis of Infection- and Vaccine-Induced B-Cell Repertoires" (2011)

Director, W.M. Keck Institute for Cellular Visualization (2009)

Humboldt Returning Fellowship (2006)

Humboldt Research Fellowship (2004)

NIH program project grant "Toward Atomic Resolution in Biological Electron Microscopy" (2001 - 2006)

Assistant in Molecular Biology - Massachusetts General Physicians Organization, Massachsetts General Hospital (2000)

Howard Hughes Medical Institute Investigator (2000 - 2001)

Medical Foundation grant "Structural Analysis of the Shaker Potassium Chanel" (2000 - 2002)

W.M. Keck Assistant Professor (1998)

Research Fellowship, Darwin College (1996)

Postdoctoral Research Fellowship, MRC Laboratory of Molecular Biology (1993 - 1998)

Courses Taught

BCHM	100a	Introductory Biochemistry
BCHM	102a	Quantitative Approaches to Biochemical Systems
BCHM	103b	Advanced Biochemistry: Information Transfer Mechanisms
BCHM	153b	Methods in High-Resolution Electron Cyro-Microscopy

Scholarship

Grigorieff, N.. "Direct detection pays off for electron cryo-microscopy." eLife 2. (2013): e00573.

Brilot, A. F., Chen, J. Z., Cheng, A., Pan, J., Harrison, S. C., Potter, C. S., Carragher, B., Henderson, R., Grigorieff, N.. "Beam-induced motion of vitrified specimen on holey carbon film." J Struct Biol 177. 3 (2012): 630-637.

Campbell, M. G., Cheng, A., Brilot, A. F., Moeller, A., Lyumkis, D., Veesler, D., Pan, J., Harrison, S. C., Potter, C. S., Carragher, B., Grigorieff, N.. "Movies of ice-embedded particles enhance resolution in electron cryo-microscopy." Structure 20. 11 (2012): 1823-1828.

Deaconescu, A. M., Artsimovitch, I., Grigorieff, N.. "Interplay of DNA repair with transcription: from structures to mechanisms." Trends Biochem Sci. 37. 12 (2012): 543-552.

Deaconescu, A. M., Sevostyanova, A., Artsimovitch, I., Grigorieff, N.. "Nucleotide excision repair (NER) machinery recruitment by the transcription-repair coupling factor involves unmasking of a conserved intramolecular interface." Proc Natl Acad Sci U S A 109. 9 (2012): 3353-8.

Estrozi, L. F., Settembre, E. C., Goret, G., McClain, B., Zhang, X., Chen, J. Z., Grigorieff, N., Harrison, S.C.. "Location of the dsRNA-dependent polymerase, VP1, in rotavirus particles." J. Mol. Biol. 425. 1 (2012): 124-132.

Henderson, R., Sali, A., Baker, M. L., Carragher, B., Devkota, B., Downing, K. H., Egelman, E. H., Feng, Z., Frank, J., Grigorieff, N., Jiang, W., Ludtke, S. J., Medalia, O., Penczek, P. A., Rosenthal, P. B., Rossmann, M. G., Schmid, M. F., Schroder, G. "Outcome of the first electron microscopy validation task force meeting." Structure 20. 2 (2012): 205-14.

Sindelar, C. V., Grigorieff, N.. "Optimal noise reduction in 3D reconstructions of single particles using a volume-normalized filter." J. Struct. Biol. 180. 1 (2012): 26-38.

Veesler, D., Quispe, J., Grigorieff, N., Potter, C. S., Carragher, B., Johnson, J. E.. "Maturation in action: cryoEM study of a viral capsid caught during expansion." Structure 20. 8 (2012): 1384-1390.

Fandrich, M., Schmidt, M., Grigorieff, N.. "Recent progress in understanding Alzheimer's beta-amyloid structures." Trends Biochem Sci 36. 6 (2011): 338-45.

Grigorieff, N., Harrison, S. C.. "Near-atomic resolution reconstructions of icosahedral viruses from electron cryo-microscopy." Curr Opin Struct Biol (2011).

Henderson, R., Chen, S., Chen, J. Z., Grigorieff, N., Passmore, L. A., Ciccarelli, L., Rubinstein, J. L., Crowther, R. A., Stewart, P. L., Rosenthal, P. B.. "Tilt-pair analysis of images from a range of different specimens in single-particle electron cryomicroscopy." J Mol Biol 413. 5 (2011): 1028-46.

Lewandowski, J. R., van der Wel, P. C., Rigney, M., Grigorieff, N., Griffin, R. G.. "Structural complexity of a composite amyloid fibril." J Am Chem Soc 133. 37 (2011): 14686-98.

Settembre, E. C., Chen, J. Z., Dormitzer, P. R., Grigorieff, N., Harrison, S. C.. "Atomic model of an infectious rotavirus particle." EMBO J 30. 2 (2011): 408-16.

Sindelar, C. V., Grigorieff, N.. "An adaptation of the Wiener filter suitable for analyzing images of isolated single particles." J Struct Biol 176. 1 (2011): 60-74.

Alushin, G. M., Ramey, V. H., Pasqualato, S., Ball, D. A., Grigorieff, N., Musacchio, A., Nogales, E.. "The Ndc80 kinetochore complex forms oligomeric arrays along microtubules." Nature 467. 7317 (2010): 805-10.

Chen, J. Z., Settembre, E., Aoki, S. T., Zhang, X., Bellamy, A. R., Dormitzer, P. R., Harrison, S. C. & Grigorieff, N.. "Molecular interactions in rotavirus assembly and uncoating seen by high-resolution cryo-EM." Proceedings of the National Academy of Sciences 106. 26 (2010): 10644-10648.

Li, X., Grigorieff, N., Cheng, Y.. "GPU-enabled FREALIGN: accelerating single particle 3D reconstruction and refinement in Fourier space on graphics processors." J Struct Biol 172. 3 (2010): 407-12.

Okada, K., Bartolini, F., Deaconescu, A. M., Moseley, J. B., Dogic, Z., Grigorieff, N., Gundersen, G. G., Goode, B. L.. "Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1." J Cell Biol 189. 7 (2010): 1087-96.

Sachse, C., Grigorieff, N. & Fändrich, M.. "Nanoscale flexibility parameters of Alzheimer amyloid fibrils determined using electron cryo-microscopy." Angewandte Chemie (International Edition) 49. 7 (2010): 1321-1323.

Schmidt. M., Sachse, C., Richter, W., Xu, C., Fändrich, M. & Grigorieff, N.. "Comparison of Alzheimer Aß(1-40) and Aß(1-42) amyloid fibrils reveals similar protofilament structures." Proceedings of the National Academy of Sciences 106. 47 (2010): 19813-19818.

Wolf, M., Garcea, R. L., Grigorieff, N. & Harrison, S. C.. "Subunit interactions in bovine papillomavirus." Proceedings of the National Academy of Sciences in press. (2010).

Xing, Y., Böcking, T., Wolf, M., Grigorieff, N., Kirchhausen, T. & Harrison, S. C.. "Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly." EMBO Journal 29. 3 (2010): 655-665.

Dementieva, I. S., Tereshko, V., McCrossan, Y. A., Solomaha, E., Araki, D., Xu, C., Grigorieff, N. & Goldstein, S. A. N.. "Pentameric assembly of potassium channel tetramerization domain-containing protein 5 (KCTD5)." Journal of Molecular Biology 387. 1 (2009): 175-191.

Fändrich, M., Meinhardt, J. & Grigorieff, N.. "Structural polymorphism of Alzheimer Aß and other amyloid fibrils." Prion 3. 2 (2009): 89-93.

Meinhardt, J., Sachse, C., Hortschansky, P., Grigorieff, N. & Fändrich, M.. "Aß(1-40) fibril polymorphism implies diverse interaction patterns in amyloid fibril." Journal of Molecular Biology 386. 3 (2009): 869-77.

Sachse, C., Grigorieff, N. & Fändrich, M.. "Elektronenmikroskopie an Alzheimer-Fibrillen." Bioforum 32. 1 (2009): 26-28.

Stroupe, M. E., Xu, C., Goode, B. L. & Grigorieff. N.. "Actin filament labels for localizing protein components in large complexes viewed by electron microscopy." RNA 15. 2 (2009): 244-248.

Chen, J. Z., Sachse, C., Xu, C., Mielke, T., Spahn, C. M. T. & Grigorieff, N.. "A Dose-Rate Effect in Single-Particle Electron Microscope." Journal of Structural Biology 161. 1 (2008): 92-100.

Sachse, C., Fändrich, M. & Grigorieff, N.. "Paired ß-sheet structure of an Aß(1-40) amyloid fibril revealed by electron microscopy." Proceedings of the National Academy of Sciences 105. 21 (2008): 7462-7466.

Zhang, X., Settembre, E., Xu, C., Dormitzer, P. R., Bellamy, R., Harrison, S. C. & Grigorieff, N.. "Near-atomic resolution using electron cryo-microscopy and single particle reconstruction." Proceedings of the National Academy of Sciences 105. 6 (2008): 1867-1872.

Zolotarev, A. S., Unnikrishnan, M., Shmukler, B. E., Clark, J. S., Vandorpe, D. H., Grigorieff, N., Rubin, E. J. & Alper, S. L.. "Increased sulfate uptake by E. coli overexpressing the SLC26-related SulP protein Rv1739c from Mycobacterium tuberculosis." Comparative Biochemistry and Physiology, Part A 149. 3 (2008): 255¿266.

Chen, J. Z., Grigorieff, N.. "SIGNATURE: A single-particle selection system for molecular electron microscopy." Journal of Structural Biology 157. 1 (2007): 168-173.

Grigorieff, N.. "FREALIGN: High-resolution refinement of single particle structures." Journal of Structural Biology 157. 1 (2007): 117-125.

Sachse, C., Chen, J. Z., Coureux, P.-D., Stroupe, M. E., Fändrich, M. & Grigorieff, N.. "High-resolution electron microscopy of helical specimens: a fresh look at tobacco mosaic virus.." Journal of Molecular Biology 371. 3 (2007): 812-35.

Sousa, D., Grigorieff, N.. "Ab initio resolution measurement for single particle structures." Journal of Structural Biology 157. 1 (2007): 201-210.

Zeng, X., Stahlberg, H. & Grigorieff, N.. "A maximum likelihood approach to two-dimensional crystals." Journal of Structural Biology 160. 3 (2007): 362-374.

Cheng, Y. F., Wolf, E., Larvie, M., Zak, O., Aisen, P., Grigorieff, N., Harrison, S. C., Walz, T.. "Single particle reconstructions of the transferrin-transferrin receptor complex obtained with different specimen preparation techniques." Journal of Molecular Biology 355. 5 (2006): 1048-1065.

Fotin, A., Kirchhausen, T., Grigorieff, N., Harrison, S. C., Walz, T., Cheng, Y. F.. "Structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy." Journal of Structural Biology 156. 3 (2006): 453-460.

Sachse, C., Xu, C., Wieligmann, K., Diekmann, S., Grigorieff, N., Fandrich, M.. "Quaternary structure of a mature amyloid fibril from Alzheimer's a beta(1-40) peptide." Journal of Molecular Biology 362. 2 (2006): 347-354.

Stroupe, M. E., Tange, T. O., Thomas, D. R., Moore, M. J., Grigorieff, N.. "The three-dimensional architecture of the EJC core." Journal of Molecular Biology 360. 4 (2006): 743-749.

Wolf, M., DeRosier, D. J., Grigorieff, N.. "Ewald sphere correction for single-particle electron microscopy." Ultramicroscopy 106. 4-5 (2006): 376-382.

Rodal, A. A., Sokolova, O., Robins, D. B., Daugherty, K. M., Hippenmeyer, S., Riezman, H., Grigorieff, N., Goode, B. L.. "Conformational changes in the Arp2/3 complex leading to actin nucleation." Nature Structural & Molecular Biology 12. 1 (2005): 26-31.

Fotin, A., Cheng, Y. F., Grigorieff, N., Walz, T., Harrison, S. C., Kirchhausen, T.. "Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating." Nature 432. 7017 (2004): 649-653.

Fotin, A., Cheng, Y. F., Sliz, P., Grigorieff, N., Harrison, S. C., Kirchhausen, T., Walz, T.. "Molecular model for a complete clathrin lattice from electron cryomicroscopy." Nature 432. 7017 (2004): 573-579.

Jurica, M. S., Sousa, D., Moore, M. J., Grigorieff, N.. "Three-dimensional structure of C complex spliceosomes by electron microscopy." Nature Structural & Molecular Biology 11. 3 (2004): 265-269.

Kim, L. A., Furst, J., Butler, M. H., Xu, S. H., Grigorieff, N., Goldstein, S. A. N.. "I-to channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2." Journal of Biological Chemistry 279. 7 (2004): 5549-5554.

Kim, L. A., Furst, J., Gutierrez, D., Butler, M. H., Xu, S. H., Goldstein, S. A. N., Grigorieff, N.. "Three-dimensional structure of I-to: Kv4.2-KChIP2 ion channels by electron microscopy at 21 angstrom resolution." Neuron 41. 4 (2004): 513-519.

Stewart, A., Grigorieff, N.. "Noise bias in the refinement of structures derived from single particles." Ultramicroscopy 102. 1 (2004): 67-84.

Chen, J. Z., Furst, J., Chapman, M. S., Grigorieff, N.. "Low-resolution structure refinement in electron microscopy." Journal of Structural Biology 144. 1-2 (2003): 144-151.

Furst, J., Sutton, R. B., Chen, J., Brunger, A. T., Grigorieff, N.. "Electron cryomicroscopy structure of N-ethyl maleimide sensitive factor at 11 angstrom resolution." Embo Journal 22. 17 (2003): 4365-4374.

Mindell, J. A., Grigorieff, N.. "Accurate determination of local defocus and specimen tilt in electron microscopy." Journal of Structural Biology 142. 3 (2003): 334-347.

Sokolova, O., Accardi, A., Gutierrez, D., Lau, A., Rigney, M., Grigorieff, N.. "Conformational changes in the C terminus of Shaker K+ channel bound to the rat Kv beta 2-subunit." Proceedings of the National Academy of Sciences of the United States of America 100. 22 (2003): 12607-12612.

Wolf, M., Eberhart, A., Glossmann, H., Striessnig, J., Grigorieff, N.. "Visualization of the domain structure of an L-type Ca2+ channel using electron cryo-microscopy." Journal of Molecular Biology 332. 1 (2003): 171-182.

Jurica, M. S., Licklider, L. J., Gygi, S. P., Grigorieff, N., Moore, M. J.. "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis." Rna-a Publication of the Rna Society 8. 4 (2002): 426-439.

McGovern, S. L., Caselli, E., Grigorieff, N., Shoichet, B. K.. "A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening." Journal of Medicinal Chemistry 45. 8 (2002): 1712-1722.

Pirruccello, M. M., Grigorieff, N., Mindell, J. A.. "Electron diffraction of a bacterial C1C-type chloride channel." Ion Channels: from Atomic Resolution Physiology to Functional Genomics. vol. 245 Chichester: John Wiley & Sons Ltd, 2002. 193-206.

Mindell, J. A., Maduke, M., Miller, C., Grigorieff, N.. "Projection structure of a CIC-type chloride channel at 6.5 angstrom resolution." Nature 409. 6817 (2001): 219-223.

Nogales, E., Grigorieff, N.. "Molecular machines: Putting the pieces together." Journal of Cell Biology 152. 1 (2001): F1-F10.

Sokolova, O., Kolmakova-Partensky, L., Grigorieff, N.. "Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm resolution." Structure 9. 3 (2001): 215-220.

Grigorieff, N.. "Resolution measurement in structures derived from single particles." Acta Crystallographica Section D-Biological Crystallography 56. (2000): 1270-1277.

Grigorieff, N. & Grigorieff, R. D.. "Asymptotisches Verhalten des Erwartungswertes für den größten Wert bei n unabhängigen Beobachtungen einer normalverteilten Variablen.." Reprint-Reihe Fachbereich Mathematik, Technische Universität Berlin Nr. 647. (1999): 1-5.

Grigorieff, N.. "Structure of the respiratory NADH : ubiquinone oxidoreductase (complex I)." Current Opinion in Structural Biology 9. 4 (1999): 476-483.

Lam, Y. M., Grigorieff, N., Goldbeck-Wood, G.. "Direct visualisation of micelles of Pluronic block copolymers in aqueous solution by cryo-TEM." Physical Chemistry Chemical Physics 1. 14 (1999): 3331-3334.

Grigorieff, N.. "Three-dimensional structure of bovine NADH : Ubiquinone oxidoreductase (Complex I) at 22 angstrom in ice." Journal of Molecular Biology 277. 5 (1998): 1033-1046.

Smith, C. J., Grigorieff, N., Pearse, B. M. F.. "Clathrin coats at 21 angstrom resolution: a cellular assembly designed to recycle multiple membrane receptors." Embo Journal 17. 17 (1998): 4943-4953.

Walz, T., Grigorieff, N.. "Electron crystallography of two-dimensional crystals of membrane proteins." Journal of Structural Biology 121. 2 (1998): 142-161.

Grigorieff, N., Ceska, T. A., Downing, K. H., Baldwin, J. M., Henderson, R.. "Electron-crystallographic refinement of the structure of bacteriorhodopsin." Journal of Molecular Biology 259. 3 (1996): 393-421.

Grigorieff, N., Henderson, R.. "Comparison of calculated and observed dynamical diffraction from purple membrane: Implications." Ultramicroscopy 65. 1-2 (1996): 101-107.

Grigorieff, N., Beckmann, E., Zemlin, F.. "Lipid Location in Deoxycholate-Treated Purple Membrane at 2.6 Angstrom." Journal of Molecular Biology 254. 3 (1995): 404-415.

Grigorieff, N., Cherns, D., Preston, A. R., Yates, M. J.. "Models for Termination of Crystal Boundaries in the Theory of Transmission Electron-Diffraction and Comparison with Experimental-Data." Acta Crystallographica Section A 51. (1995): 343-350.

Grigorieff, N., Henderson, R.. "Diffuse scattering in electron diffraction data from protein crystals." Ultramicroscopy 60. 2 (1995): 295-309.

Duan, X. F., Grigorieff, N., Cherns, D., Steeds, J. W., Sheng, C.. "Profiling of Gexsi1-X/Si Strained-Layer Superlattices by Large-Angle Convergent-Beam Electron-Diffraction and Electron Holography." Microscopy of Semiconducting Materials 1993. Bristol: Iop Publishing Ltd, 1993. 513-516.

Grigorieff, N., Cherns, D., Yates, M. J., Hockly, M., Perrin, S. D., Aylett, M. R.. "Electron-Microscopy of Ultra-Thin Buried Layers in Inp and Ingaas." Philosophical Magazine a-Physics of Condensed Matter Structure Defects and Mechanical Properties 68. 1 (1993): 121-136.

Jordan, I. K., Grigorieff, N., Cherns, D., Hockly, M., Spurdens, P. C., Aylett, M. R., Scott, E. G.. "The Detection of Strain within Inp-Ingaas Single Quantum-Well Structures Using Large-Angle Convergent Beam Electron-Diffraction." Institute of Physics Conference Series 117 (1991): 563-568.