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Three-part handoff delivers proteins to membrane surface
Date:8/24/2011

says is "like Dr. Octopus."

3. Next, Get2 executes a football-style handoff to the adjacent Get1 protein. Binding to Get1 causes the two Get3s to partially "unzip," wedging open the groove and releasing the tail-anchored substrate for insertion into the membrane.

4. Finally, new ATP molecules bind to Get3 causing it to zip back up into the closed form. This releases it from Get1 so that it can initiate another round of protein delivery in the cytosol.

"We have a minimal system, completely purified, that's only three components plus the substrate," Keenan said. "Now we can basically do whatever we want. We can make mutants or chemical modifications, and then we can reconstitute the system and ask, 'does it work?' And if it doesn't work, we can ask where in this process does it actually fail, and why."

Some steps of the pathway remain incomplete, such as how the tail-anchor of the protein is finally inserted into the membrane after it is released by Get3. But with the purified system, researchers can begin exploring these questions, and comparing the TA protein pathway to the more complex co-translational pathway.

As the delivery systems for proteins of all types are better understood, scientists can then use these systems to create better drugs and manipulate cells for bioengineering purposes. For example, some viruses are thought to exploit protein delivery pathways, and understanding the details of trafficking may suggest new ways of defending cells against infection.

"The more we understand about different targeting pathways, the better our ability to successfully target proteins where we want," Keenan said. "Right now, there's no killer app, but you can imagine a lot of potential uses."


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Contact: Robert Mitchum
robert.mitchum@uchospitals.edu
773-795-5227
University of Chicago Medical Center
Source:Eurekalert

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