Frank Lab

Welcome to the Frank Lab

We investigate the mechanism of translation on the ribosome by using cryo-electron microscopy and single-particle reconstruction.

Recent Publications

Book: Found in Translation: Collection of Original Articles on Single-Particle Reconstruction and the Structural Basis of
Protein Synthesis
Publisher: World Scientific
[Description]

Book: Computational Methods for Three-Dimensional
Microscopy Reconstruction
Editors: Garbor T. Herman, Joachim Frank
Publisher: Springer
[Description]

Article: Exploring the dynamics of supramolecular machines with
cryo-electron microscopy
Journal: International Solvay Institutes
Author: Joachim Frank
[Introduction]

Article: EttA regulates translation by binding to the ribosomal E site and restricting ribosome-tRNA dynamics
Journal: Nature Structural & Molecular Biology
Author: Bo Chen, et al.
[Abstract]

Article: The ABC-F protein EttA gates ribosome entry into the translation elongation cycle
Journal: Nature Structural & Molecular Biology
Author: Grégory Boël, et al.
[Abstract]

Article: Structure of the mammalian ribosomal pre-termination complex associated with eRF1•eRF3•GDPNP
Journal: Nucleic Acids Research
Author: Amédée des Georges, et al.
[Abstract]

Article: Hepatitis-C-virus-like internal ribosome entry sites displace eIF3 to
gain access to the 40S subunit
Journal: Nature
Author: Yaser Hashem, et al.
[Abstract]

Article: Cryo-EM visualization of the ribosome in termination complex
with apo-RF3 and RF1
Journal: eLife
Author: Jesper Pallesen, et al.
[Abstract]

Article: Structure of the mammalian ribosomal 43S preinitiation complex
bound to the scanning factor DHX29
Journal: Cell
Author: Yaser Hashem, et al.
[Summary]

Article: Story in a sample – the potential (and limitations) of cryo-electron microscopy applied to molecular machines
Journal: Biopolymers
Author: Joachim Frank
[Introduction]

Molecular machines are workshops in the cell that bring molecules and substrates together in a coordinated, processive way.1‐2. The molecular complexes acting as molecular machines are often spatially localized and assembled in an ad‐hoc fashion, in response to the demands of the cell’s metabolism. Products of such binding reactions can be RNA or DNA polymers, ATP, or other compounds needed at the site. Well‐known examples are RNA and DNA polymerases, ATP synthase, the ribosome, and the proteasome. Visualizing molecular machines in their various states of processing poses challenges which traditional techniques of structure research find hard to meet. The complexes formed in the course of the work cycle are typically large, relatively unstable, and flexible ‐‐ all properties that disfavor X‐ray crystallography as a means of visualization. In addition, molecular machines can have multiple binding partners and can go through numerous states, characterized by different conformations and binding configurations. Purification of such complexes can be done through two different routes: either from a cell extract or from an in vitro reconstituted system. In either case, it is difficult to isolate the complex by biochemical means in one of its many states with the purity required for structural research. Cryo‐electron microscopy (cryo‐EM) is a fairly new technique for obtaining a 3D image of a molecule from a large set of projections, harvested from micrographs of a field of molecules captured in random orientations.3 In some cases, resolutions in the range of 4 to 5.5 Å have already been achieved for the ribosome, an RNA‐containing molecular machine.4‐6 Purity of the sample in terms of conformation and binding state of the molecule is evidently an absolute requirement for obtaining a meaningful 3D image from the “single particle” projection data set. In certain cases, high purity can be achieved by affinity imaging techniques.7‐9 However, because of inherent difficulties of finding biochemical methods that guarantee 100% purity, it has been a goal in the development of cryo‐EM to accomplish the purification of the molecules after the imaging, at the data processing step. Cryo‐EM projection data have a typical signal‐to‐noise ratio in the order of 0.1 or even less.10 The challenge posed by classification of such noisy data is compounded by the fact that variability stemming from a change in viewing direction is intermingled with variability due to heterogeneity of composition or conformation.

Recent News

New paper in Nucleic Acids Research journal

February 4, 2014

Structure of the mammalian ribosomal pre-termination complex associated with eRF1•eRF3•GDPNP des Georges, A., Hashem, Y., Unbehaun, A., Grassucci, R.A., Taylor, D., Hellen, C.U.T., Pestova, T.V., and Frank, J. Abstract: Eukaryotic translation termination results from the complex functional interplay between two release factors, eRF1 and eRF3, in which GTP hydrolysis by eRF3 couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, we present a cryo-electron microscopy structure of pre-termination complexes associated with...

Welcome to the Frank Lab

Recent Publications

Recent News

New paper in Nucleic Acids Research journal

Book: Found In Translation

Solvay Institute archival letters

Franklin Institute Award announcement

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