DNA conformational changes play a force-generating role during bacteriophage genome packaging

A paper titled DNA Conformational Changes Play a Force-Generating Role during Bacteriophage Genome Packaging has just been officially published in the Biophysical Journal (Volume 116, Issue 11, P2172-2180, June 04, 2019). I am glad to have the opportunity to collaborate with Kim Sharp, Gino Cingolani and Stephen Harvey on this interesting project that has big implications in understanding the mechanism of bacteriophage genome packaging. The abstract of the paper is shown below:

Motors that move DNA, or that move along DNA, play essential roles in DNA replication, transcription, recombination, and chromosome segregation. The mechanisms by which these DNA translocases operate remain largely unknown. Some double-stranded DNA (dsDNA) viruses use an ATP-dependent motor to drive DNA into preformed capsids. These include several human pathogens as well as dsDNA bacteriophages—viruses that infect bacteria. We previously proposed that DNA is not a passive substrate of bacteriophage packaging motors but is instead an active component of the machinery. We carried out computational studies on dsDNA in the channels of viral portal proteins, and they reveal DNA conformational changes consistent with that hypothesis. dsDNA becomes longer (“stretched”) in regions of high negative electrostatic potential and shorter (“scrunched”) in regions of high positive potential. These results suggest a mechanism that electrostatically couples the energy released by ATP hydrolysis to DNA translocation: The chemical cycle of ATP binding, hydrolysis, and product release drives a cycle of protein conformational changes. This produces changes in the electrostatic potential in the channel through the portal, and these drive cyclic changes in the length of dsDNA as the phosphate groups respond to the protein’s electrostatic potential. The DNA motions are captured by a coordinated protein-DNA grip-and-release cycle to produce DNA translocation. In short, the ATPase, portal, and dsDNA work synergistically to promote genome packaging.

Significantly, our work is highlighted in a “New and Notable” article, May the Road Rise to Meet You: DNA Deformation May Drive DNA Translocation by Paul Jardine (Volume 116, Issue 11, Pages 2060-2061, 4 June 2019):

Regardless of what drives conformational change in the portal, the idea that the linear DNA substrate is deformed in a way that makes it an energetic participant in its own movement opens new possibilities for how motors work. Large paddling or rotational motions by motor components may not be required if linear motion can be achieved by stretching or compressing the linear substrate, with rectified, cyclic conformational changes in the DNA rather than lever motions doing the work. If borne out by experiments, further simulation, and more structural information, this proposed mechanism may require a reappraisal of how we think about translocating motors.

For this project, I developed the x3dna-search program to survey similar fragments of single-stranded or double helical structures in the PDB.

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Comment

The Double Helix is wrong: there is no mutual twisting of the two strands — they run in parallel. I proposed a different model, it is described in the article:
http://vixra.org/abs/1803.0104
I hope it will be interesting for you.

Lev · 2019-06-08 11:03 · #

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Hi Lev,

Thanks for your comment and your interesting article. It is a nice perspective. However, I cannot agree to your conclusion that “The Double Helix is wrong: there is no mutual twisting of the two strands — they run in parallel.” The many DNA-containing structures determined experimentally in the PDB are double-helical, as proposed by Watson-Crick.

Xiang-Jun

— Xiang-Jun Lu · 2019-06-08 11:38 · #

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Commenting is closed for this article.

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