Modeling How Proteins Interact With DNA

Editor's Choice
Main Category: Biology / Biochemistry
Also Included In: Genetics
Article Date: 01 Oct 2008 - 0:00 PST

email to a friend   printer friendly   view / write opinions   rate article

An article published in the open-access journal PLoS Biology reports on DNA loop formation - one very important process in the regulation of gene expression. Researchers from Brandeis University used state-of-the-art tools to observe a protein involved in regulating DNA transcription. Lac repressor is a protein from the bacterium E. coli that turns individual genes on and off, and researchers were able to analyze the shape and behavior of the protein as it bent individual DNA molecules into tight loops.

A protein must create a DNA loop and bind to two different places on the gene at the same time in order to switch certain genes on or off. The features of these loops are not well understood, even though they are quite common. The Brandeis researchers used atomic force microscopy and tethered particle motion (TPM) to look at single molecules of DNA. This allowed them to understand the shape of the loop, something that is otherwise not visible. Their findings suggested that many previous models of DNA loops were probably incorrect. This earlier research required the DNA to bend and twist in ways that are incompatible with the behaviors observed when studying the single DNA molecules.

The researchers were able to view the shape of the DNA molecules by using atomic force microscopy, and they were able to note the behavior of the molecules by using TPM. Attaching a tiny plastic bead (one millionth of an inch in diameter) to the end of a DNA molecule, the TPM experiments allowed a computer to analyze bead movements that were seen in a microscope. As the DNA looped and unlooped, scientists monitored the details of the molecule's behavior.

These techniques are all very sophisticated, but the researchers also created simple 3-D models of the DNA loops. They visualized how the protein bent and twisted DNA using binder clips and tape. This aided in determining which models were possible and which were unlikely.

"What we demonstrated in this paper is that, contrary to what many scientists thought, the structure of the protein is flexible and can take on different shapes, helping to minimize DNA bending or twisting in loops, and thus, maximize stable gene regulation," said Professor Jeff Gelles. "We believe the protein has the ability to change its shape to accommodate different sized loops and different amounts of DNA, helping cells
maintain genes in a switched on or switched off state."

"We think it is possible that the characteristics of this genetic switch are examples of a general phenomenon that helps explain gene regulation," Gelles added. It is known that many disease and cancers are linked to poor gene regulation; an understanding of how it works - even a simple bacterium - may help future antibiotic development.

"The key is that the protein can change shape 'on the fly' to accommodate different kinds of loops, or different spacing between different parts of the DNA. This is the way that the protein may have evolved to make gene regulation more reliable," concludes Gelles.

Interconvertible Lac repressor-DNA loops revealed by single-molecule experiments
Wong OK, Guthold M, Erie DA, Gelles J
PLoS Biology (2008). 6(9): e232.
doi:10.1371/journal.pbio.0060232
Click Here to View Article

About PLoS Biology

PLoS Biology is an open-access, peer-reviewed general biology journal published by the Public Library of Science (PLoS), a nonprofit organization of scientists and physicians committed to making the world's scientific and medical literature a public resource. New articles are published online weekly; issues are published monthly. For more information, visit http://www.plosbiology.org

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org

Written by: Peter M Crosta
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today