News

Two promising future developments of cryo-EM: capturing short-lived states and mapping a continuum of states of a macromolecule. Bo Chen and Joachim Frank ABSTRACT: The capabilities and application range of cryogenic electron microscopy (cryo-EM) method have expanded vastly in the last two years, thanks to the advances provided by direct detection devices and computational classification tools. We take this review as an opportunity to sketch out promising developments of cryo-EM in two important directions: (1) imaging of short-lived states (10 ms – 1000 ms) of biological molecules by using...

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Breaking the Crystal Ceiling: Cryo-electron microscopy goes high resolution. By Erika Gebel Berg ACS Central Science The king and queen of protein structure determination have, for years, been X-ray crystallography and nuclear magnetic resonance spectroscopy. But now there’s a challenger to the throne. This upstart is cryo-electron microscopy (EM)... Click here to read more.

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In my attempts to make sense of some of the recent commentaries about single-particle cryo-EM, I found much earlier evidence of excitement about the technique. Arthur Robinson, in a 1976
Research News article published in Science entitled “Electron Microscopy: Imaging Molecules in Three Dimensions,” starts by explaining the principles of 3D reconstruction using Jim Lake’s now-familiar cartoon with ducks and their transforms. The article then goes on with an appreciation...

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A new paper has just been accepted by NAR journal. Dynamical features of the Plasmodium falciparum ribosome during translation. Ming Sun, Wen Li, Karin Blomqvist, Sanchaita Das, Yaser Hashem, Jeffrey D. Dvorin, & Joachim Frank.
ABSTRACT: Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the most severe form of human malaria. In the asexual blood-stage, the parasite resides within erythrocytes where it proliferates, multiplies and finally spreads to new erythrocytes....

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A new paper has recently been accepted by Nature–"Structure of mammalian eIF3 in the context of the 43S preinitiation complex" by Amedee Des Georges, Vidya Dhote, Lauriane Kuhn, Christopher U. T. Hellen, Tatyana V. Pestova, Joachim Frank & Yaser Hashem. ABSTRACT: During eukaryotic translation initiation, 43S complexes, comprising a 40S ribosomal subunit, initiator transfer RNA and initiation factors (eIF) 2, 3, 1 and 1A, attach to the 5′-terminal region of messenger RNA and scan along it to the initiation codon. Scanning on structured mRNAs also requires the DExH-box protein DHX29. Mammalian...

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Frank Lab celebrated with ribosome cookies, baked by Andrey Malyutin. He described how he engineered the conformational changes. "Since the dough is relatively warm and very flexible at the time, just the variations in how I pick up the cut out and place it on a cookie sheet results in semi-random variation in the cookie shape. Particularly the thin, flexible regions, such as the stalk end up being distorted compared to the mold shape, resulting in open, closed, and intermediate structures."
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Frank Lab post doc, Amédée Des Georges, has been named Assistant Professor with the Structural Biology Initiative at CUNY's newly constructed Advanced Science Research Center (ASRC) located at 85 St. Nicholas Terrace.
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The June 2015 cover of Structure is an illustration by Melissa Thomas-Baum and Hstau Y. Liao. It accompanies this article published in the same issue: Liao, H.Y., Hashem, Y., and Frank, J. (2015). Efficient estimation of three-dimensional covariance...

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The real-space 3D covariance estimation we published recently constitutes a very significant advance in methodology (Liao et al., 2015). In a heterogeneous dataset of a molecular machine such as the ribosome one would wish to identify and locate interdependencies between movements of different domains and the binding of functional ligands. These interdependencies can be expressed by the variance/covariance matrix, a matrix with N x N entries if N is the total number of voxels. Diagonal elements are those of the 3D variance components. The normal inquiry would be confined to the contents of a single...

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A paper entitled “Structural dynamics of ribosome subunit association studied by mixing-spraying time-resolved cryo-EM” by Bo Chen, Sandip Kaledhonkar, Ming Sun, Bingxin Shen, Zonghuan Lu, David Barnard, Toh-Ming Lu, Ruben L. Gonzalez Jr., and Joachim Frank has just been accepted by the journal Structure. The study follows the reaction at time points 60 and 140 milliseconds, and two several minutes long controls. Contentious questions to be answered were: At what time are bridges formed? Does the association reaction follow kinetic predictions? In what states (rotated vs. unrotated) are the newly...

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