Toe in the water for Emory cryo-EM structures

Congratulations to Christine Dunham and colleagues in the Department of Biochemistry for their first cryo-electron microscopy paper, recently published in the journal Structure.

The paper solves the structure of a bacterial ribosome bound to a messenger RNA containing a loop that regulates translation. This process is important for the study of several neurological diseases such as fragile X syndrome, for example.

Christine Dunham, PhD

Dunham writes: “We are focusing on establishing this in bacteria to understand frameshifting and protein folding as a consequence of codon preference. We will then build up our knowledge to potentially study eukaryotic translational control.”

The paper neatly links up with two Nobel Prizes: the 2017 Chemistry prize for cryo-electron microscopy and the 2009 Chemistry prize for ribosome structure, awarded in part to Dunham’s mentor Venki Ramakrishnan. Also, see this 2015 feature from Nature’s Ewen Callaway outlining how cryo-EM is a must have for structural biologists wanting to probe large molecules that are difficult to crystallize.

Construction now underway in the Biochemistry Connector will allow installation of microscopes (worth $6 million) necessary for Dunham and others to do cryo-EM here at Emory, although she advises that it will be several months until they are photo-op ready. For the Structure paper, Dunham collaborated with George Skiniotis at University of Michigan; he recently moved to Stanford.

From the discussion:

Our structures reveal a non-rotated ribosome with an unexpected E-tRNA conformation when the mRNA stem loop is positioned at the entrance channel… The inability to observe the Eout tRNA position in previous studies could arise from a transient nature of this conformation, which would therefore not be observed in structural studies using X-ray crystallography. However, in the presence of the downstream structured mRNA the dissociation of E-tRNA is slowed, allowing this state to be populated to a greater extent, thus explaining its visualization in our cryo-EM analysis.

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Posted on by Quinn Eastman in Neuro, Uncategorized Leave a comment

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Quinn Eastman

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