Mitochondria have proteins that span their membranes to control the flow of messages and materials moving into and out of the organelle. One way scientists can learn more about how membrane proteins function—and how medicines might interact with them—is to determine their structures. But for a variety of reasons, obtaining the structures has been notoriously difficult. Two structural studies have now shed light on the mysterious mitochondrial membrane protein TSPO. This protein plays a key role in transporting cholesterol and drugs into the cell’s mitochondria. While here, the cholesterol is converted to steroid hormones that are essential for numerous bodily functions. Although many researchers have been studying TSPO since the 1990s, they’ve remained uncertain about its mechanisms and how it truly functions.

Our cells come equipped with a self-destruct mechanism that’s activated during apoptosis, a carefully controlled process by which the body rids itself of unneeded or potentially harmful cells. Scientists have long known that a protein called PSR-1 helps clean up the cellular remains. Now they’ve found that PSR-1 also can repair broken nerve fibers.

Ding Xue of the University of Colorado, Boulder, and others made the finding in the tiny roundworm C. elegans, which scientists have used to study apoptosis and identify many of the genes that regulate the process. While apoptotic cells sent “eat me” signals to PSR-1, injured nerve cells sent “save me” signals to the protein. These SOS signals helped reconnect the broken nerve fibers, called axons, that would otherwise degenerate after an injury.

One of the items on biomedical researchers’ “to-do” list is devising noninvasive ways to control the activity of specific genes or cells in order to study what those genes or cells do and, ultimately, to treat a range of human diseases and disorders. A team of scientists recently reported progress on a new, noninvasive system that could remotely and rapidly control biological targets in living animals. The system can be activated remotely using either low-frequency radio waves or a magnetic field. Similar radio wave technology operates automatic garage-door openers and remote control car keys and is used in medicine to control electronic pacemakers noninvasively. Magnetic fields are used to activate sensors in burglar alarm systems and to turn your laptop to hibernate mode when the cover is closed.

It’s not every day that we log into Facebook and Twitter to see conversations about denaturing proteins and the possibility of reducing biotechnology costs, but that changed last week when a story about “unboiling” eggs became a trending topic. Since NIGMS partially funded the research advance that led to the media scramble, we asked our scientific expert Jean Chin to tell us more about it. What’s the advance? Gregory Weiss of the University of California, Irvine, and his collaborators have designed a device that basically unties proteins that have been tangled together.

The effects some medicines have on our salivary glands can at times extend beyond the fleeting flavor we experience upon ingesting them. Sometimes drugs cause a prolonged bad taste or dryness in the mouth, both of which can discourage people from taking medicines they need. Now, a research team led by Joanne Wang of the University of Washington has discovered a possible mechanism behind this phenomenon. Working primarily with mice and using a commonly prescribed antidiabetic drug known to impair taste, the scientists identified a protein in salivary gland cells that takes up the drug from the bloodstream and secretes it in saliva. Wang and her colleagues were also able to pinpoint a specific gene that, when removed, hindered this process. They hope their new insights will aid efforts to develop medicines that do not cause salivary issues. This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. Learn more: University of Washington News Release

Our bodies depend on a set of immune receptors to remove harmful bacteria and control the growth of helpful bacteria in our guts. Genetic changes that alter the function of the receptors can have an adverse effect and result in chronic inflammatory diseases like Crohn’s disease. Catherine Leimkuhler Grimes and Vishnu Mohanan of the University of Delaware researched a Crohn’s-associated immune receptor, NOD₂, to figure out how it can lose the ability to respond properly to bacteria. In the process, they identified the involvement of a protective protein called HSP₇₀. Increasing HSP₇₀ levels in kidney, colon and white blood cells appeared to restore NOD₂ function. This work represents a first step toward developing drugs to treat Crohn’s disease. This work was funded in part by an Institutional Development Award (IDeA) Network of Biomedical Research Excellence (INBRE) grant.

Alzheimer’s disease, type 2 diabetes and many other illnesses are linked to the buildup of proteins whose structures have changed into shapes that enable the formation of cell-entangling threads called amyloid fibrils. About 10 years ago, researchers led by Valerie Daggett of the University of Washington used computer simulations to suggest that such proteins, on their way to creating fibrils, form an intermediary structure called an alpha sheet that’s even more toxic to cells than fibrils. Now Daggett’s team has experimentally investigated this possibility. The scientists made alpha sheet molecules expected to bind to amyloid-forming proteins in the computationally predicted intermediate state. When they tested the molecules on two amyloid disease-related proteins, they observed a substantial reduction in fibril formation. The work is still very preliminary, but it highlights a potential new avenue for treating a range of amyloid-related diseases. This work also was funded by NIH’s National Institute of Allergy and Infectious Diseases. Learn more: University of Washington News Release Daggett Lab Monster Mash: Protein Folding Gone Wrong Article from Inside Life Science

Meet dynein, the August Molecule of the Month presented by the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). This motor protein travels along the cables of our cellular skeleton, delivering cargo throughout the cell. The structure of dynein’s stalk enables it to bind to regular grooves along its path. Dynein’s shape is just one of more than 100,000 structures that scientists have deposited in the PDB archive, a freely available digital repository. Because understanding a protein’s shape helps researchers better understand its function, the structural information in the PDB can lead to additional scientific advancements. For example, scientists use the structure of HIV protease, a protein that helps the virus replicate in the body, to develop drugs that fit snugly into the protein’s center, shutting it down. And they use the shape of RNA polymerase to learn how this protein fits together with smaller ones to read our genetic code. The PDB has doubled in size over the last 6 years. As the collection continues to grow, so does our potential for drug discovery and our understanding of basic life processes. Learn more: Molecule of the Month Archive from RCSB PDB

As the temperature climbs, most humans look for ways to cool down fast. But for some species of microorganisms, a midsummer heat wave isn’t nearly hot enough. These heat lovers, known as thermophiles, thrive at temperatures of 113°F or more. They’re often found in hot springs, geysers and even home water heaters. Like humans and other organisms, thermophiles rely on proteins to maintain normal cell function. While our protein molecules break down under intense heat, a thermophile’s proteins actually work more efficiently. They also tend to be more stable at room temperature than our own. An NIH-funded research team is taking advantage of this property of thermophiles to better understand a group of human proteins commonly targeted by today’s medicines. Read more about the team’s thermophile research in this Inside Life Science article.

LovD9, a mutated version of an enzyme extracted from mold growing in soil, produces the cholesterol-reducing drug simvastatin 1,000 times faster than its natural predecessor. But scientists didn’t understand why because the enzyme’s mutations are far from the active site, where the drug is actually made. Now they do. Yi Tang of the University of California, Los Angeles (UCLA), in partnership with the pharmaceutical company Codexis, generated LovD9 by repeatedly inducing random mutations, each time selecting the mutated versions of the enzyme with the most promise for industrial simvastatin production. Then, the team collaborated with UCLA colleagues Kendall Houk and Todd Yeates to unlock the secret of the enzyme’s speed. Using ANTON, a special-purpose supercomputer at the Pittsburgh Supercomputing Center, they simulated how different parts of the enzyme rotate and twist when synthesizing the drug. The scientists discovered that as LovD9 moves, it forms shapes that facilitate simvastatin production more often than the natural enzyme does. With their better understanding of how mutations far from an active site may affect an enzyme’s motion, the researchers hope to one day directly engineer enzymes with precise mutations that enhance drug production. Learn more: University of California, Los Angeles News Release Houk , Tang and Yeates Labs