Electron cryo-microscopy of non-crystalline protein preparations (single particles) is rapidly becoming one of the most versatile and powerful techniques for the determination of the 3D structure of proteins. Current state-of-the-art electron microscopes and image processing have produced structures of protein complexes at 7A resolution. However, projections of the physical limits of this technique indicate near-atomic resolution can be achieved. The goal of this project is to develop new image processing algorithms to approach the physical limits as closely as possible. Specifically, a quantitative description of image contrast will be derived using well-studied specimens with an existing atomic model. Second, and key to high resolution, more powerful methods for the refinement of particle alignments will be developed based on maximum likelihood principles. Third, a reliable measure of resolution will be defined to serve as a hard quality measure for structures solved by single particle methods. Last, the new single particle algorithms will be put into a general form to extend their application to the alignment of unit cells in 2-dimensional crystals. The new set of programs will thus be universally applicable to ordered specimens, partially disordered specimens, and non- ordered preparations, yielding a structure at the best possible resolution in each case.
| Close, William; Neumann, Matthias; Schmidt, Andreas et al. (2018) Physical basis of amyloid fibril polymorphism. Nat Commun 9:699 |
| Liu, Yuhang; Pan, Junhua; Jenni, Simon et al. (2017) CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody-Antigen Interface. J Mol Biol 429:1829-1839 |
| Loveland, Anna B; Demo, Gabriel; Grigorieff, Nikolaus et al. (2017) Ensemble cryo-EM elucidates the mechanism of translation fidelity. Nature 546:113-117 |
| Abeyrathne, Priyanka D; Koh, Cha San; Grant, Timothy et al. (2016) Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome. Elife 5: |
| Schmidt, Andreas; Annamalai, Karthikeyan; Schmidt, Matthias et al. (2016) Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril. Proc Natl Acad Sci U S A 113:6200-5 |
| Chou, Hui-Ting; Dukovski, Danijela; Chambers, Melissa G et al. (2016) CATCHR, HOPS and CORVET tethering complexes share a similar architecture. Nat Struct Mol Biol 23:761-3 |
| Dimitrova, Yoana N; Jenni, Simon; Valverde, Roberto et al. (2016) Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore Assembly. Cell 167:1014-1027.e12 |
| van der Feltz, Clarisse; Pomeranz Krummel, Daniel (2016) Purification of Native Complexes for Structural Study Using a Tandem Affinity Tag Method. J Vis Exp : |
| Loveland, Anna B; Bah, Eugene; Madireddy, Rohini et al. (2016) Ribosome•RelA structures reveal the mechanism of stringent response activation. Elife 5: |
| Baytshtok, Vladimir; Fei, Xue; Grant, Robert A et al. (2016) A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis. Structure 24:1766-1777 |
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