Biomedical Beat - A monthly digest of research news from NIGMS

IN THIS ISSUE . . .
June 18, 2008

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The National Institute of General Medical Sciences (NIGMS), one of the National Institutes of Health, supports all research featured in this digest. Although only the lead scientists are named, coworkers and other collaborators also contributed to the findings. To read additional news items, visit NIGMS News. To check out free NIGMS publications, go to the order form.

Cool Movie: Folding Proteins

The lid of this barrel-shaped molecule opens and closes to control how proteins fold into the unique shapes that determine their function. The lid of this barrel-shaped molecule opens and closes to control how proteins fold into the unique shapes that determine their function.

Full movie
Caption: Movie of folding proteins

Note: You may need to download the free Quicktime player to view the movie.

Like the iris in a camera lens that controls light, the lid of this barrel-shaped molecule opens and closes to control how proteins fold into the unique shapes that determine their function. The exact manner by which proteins fold has been a mystery. Scientists knew that some proteins fold inside these molecules, called chaperonins, but they couldn’t see how. This movie of the chaperonin TRiC literally unlocks the door, showing that the opening’s widening and narrowing dictates how proteins fold or unfold. The advance also offers new details on how a protein lines up inside the chaperonin and folds once the door closes. Courtesy of molecular biologist Judith Frydman, Stanford University.

This work also was supported by the NIH Roadmap for Medical Research.

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Frydman lab home page
Article abstract (from the June 8 online issue of Nature Structure Molecular Biology)

The Skinny on Enzymes in Appetite Control

Role of CaMKK2 in the pathway regulating appetite and glucose levels. Courtesy of Anthony Means.
Role of CaMKK2 in the pathway regulating appetite and glucose levels. Courtesy of Anthony Means.
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Many people are always looking for ways to lose weight and control their appetite and blood sugar levels. Endocrinologist Anthony Means and his team of researchers at Duke University Medical Center have been, too—but in mice. The team studied the brain enzyme CaMKK2, known to activate another enzyme involved in appetite stimulation. When Means and colleagues blocked CaMKK2 activity in mice that normally produce the enzyme, they found that the rodents ate less and lost weight. They also saw that the absence of CaMKK2 improved glucose tolerance and insulin sensitivity. Although preliminary, the results point to a potential drug target for appetite control, weight loss, and blood sugar management.

NIH’s National Institute of Diabetes and Digestive and Kidney Diseases also supported this work.

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Means home page
Article abstract (from the May 7 issue of Cell Metabolism)

Compound Offers Potential Lead for New AIDS Drug

Animation of molecule that inhibits HIV-1 protease. Courtesy of Kelly Damm. Animation of molecule that inhibits HIV-1 protease. Courtesy of Kelly Damm.
Full movie
Animation of molecule that inhibits HIV-1 protease. Courtesy of Kelly Damm.

Note: You may need to download the free Quicktime player to view the movie.

More than a million Americans are living with HIV/AIDS. Their survival depends largely on drugs called protease inhibitors that prevent the virus from maturing and replicating. Some of the efforts to improve treatment have focused on finding other ways to disable the HIV-1 protease enzyme. A new lead comes from University of Michigan chemist Heather Carlson. Using computer models, the Carlson group developed a small molecule that blocked HIV-1 protease activity in a manner different from existing drug treatments. More research needs to be done, but the work could guide the way for developing a new class of AIDS drugs.

Full story
Carlson lab home page
Article abstract (from the August issue of Biopolymers)

Vitamin Tunes Up Gene Activity

Video interview with Jasper Rine. Courtesy of UC Berkeley.
Watch the video interview with Jasper Rine. Courtesy of UC Berkeley.

Researchers led by geneticist Jasper Rine of the University of California, Berkeley, have found another reason to delve into your genes. Using yeast as an experimental tool to study the expression of human genetic variants, Rine’s team discovered that a vitamin supplement can tune up the activity of a human enzyme. The study focused on variants of an enzyme that requires folate to function properly. The researchers expressed the gene variants in yeast and added more folate to the organisms’ diet, boosting the activity of nearly all the variants. While the work offers promising preliminary results, its application to human health has yet to be explored.

Full story
Rine lab home page
Article abstract (from June 10 issue of PNAS)

Molecule Clears Brain Clumps

Amyloid fibers without (left) and with (right) DAPH treatment. Courtesy of James Shorter.
Amyloid fibers without (left) and with (right) DAPH treatment. Courtesy of James Shorter.
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Protein fibers in the brain can misfold and form amyloid plaques that clutter nerve cells and trigger Alzheimer’s disease and other neurodegenerative disorders. Things may clear up, however, with recent discoveries by a team led in part by Massachusetts Institute of Technology molecular biologist Susan Lindquist. The researchers found that the small molecule DAPH selectively targeted amyloid fibers made from ABeta peptide—the toxic peptide in Alzheimer’s disease—and converted them to a form unable to grow. DAPH also worked on yeast amyloid proteins. Dismantling these fibers could influence the development of treatments for a host of neurodegenerative diseases.

NIH’s National Institute on Aging also supported this work.

Full story
Lindquist lab home page
Article abstract (from the May 20 issue of PNAS)