Proteins, the biological molecules that are involved in virtually every action of every organism, may themselves move in surprising ways, according to a recent study from the U.S. Department of Energy’s Argonne National Laboratory that may shed new light on how proteins interact with drugs and other small molecules.

This study, which relied on the intense X-ray beams available at Argonne’s Advanced Photon Source, uses a new approach to characterize the ways in which proteins move around in solution to interact with other molecules, including drugs, metabolites or pieces of DNA.

“Proteins are not static, they’re dynamic,” said Argonne biochemist Lee Makowski, who headed the project. “Part of the common conception of proteins as rigid bodies comes from the fact that we know huge amounts about protein structures but much less about how they move.”

The study of proteins had long focused almost exclusively on their structures, parts of which can resemble chains, sheets or …

The ubiquitin proteasome system (UPS) is part of the waste management system of a cell. Proteins that are destined to have limited life spans in the cell are identified and sorted for destruction. This is accomplished by labeling the proteins with the molecule ubiquitin, which is present in all eukaryotes. Once tagged, the proteins are degraded by a complex machine known as the proteasome. The UPS is not just a molecular wood chipper; it performs its function with specificity that is provided by the class of ubiquitination enzymes called E3 ligases. The E3 ligases identify proteins to be degraded through domains called F-boxes, but the mechanism of enzymatic transfer of ubiquitin to the doomed protein is still not completely understood and may be facilitated by the dimerization of another domain, known as the D-domain. In studies carried out at the NE-CAT 8-BM-B, BioCars 14-BM-C, BioCAT 18-ID-D, and SBC-CAT 19-BM-D …

It has been known that muscle fibers shorten slowly under heavier loads and faster under lighter loads. Now, researchers from the Università degli Studi di Firenze, Università di Roma, Dexela Ltd., the Illinois Institute of Technology, and King’s College London, using the BioCAT 18-IDD beamline at the APS have discovered the molecular basis of this fundamental property of muscle function. Their work was the cover article for the issue of Cell magazine in which it was published. Understanding exactly how muscle fibers work …

The stars of muscle contraction—be it the flex of a bicep or the throb of the heart—are microscopic fibers spun from the proteins actin and myosin. To play their parts properly, these proteins need help from an additional, less well-understood molecule known as myosin-binding protein-C. Thanks to data collected at BioCAT beamline 18-ID-D at the APS, researchers from the University of Wisconsin Medical School and the Illinois Institute of Technology have gleaned insights into this protein’s contribution to a smoothly beating heart.

Heart muscle fibers, like those of skeletal muscle, consist of alternating sets of parallel filaments. Thick filaments, which are bundles of myosin molecules, overlap at each end with thin filaments composed of small actin molecules. Connecting the …

A drug normally used to treat Alzheimer’s disease may act as a “copper bullet,” killing tumor cells by coating itself in copper ions, according to research derived in part from studies at the APS. Researchers from Wayne State University, the Henry Ford Hospital, the Illinois Institute of Technology, and Shandong University using BioCAT beamline 18-ID-D at the APS found that the drug clioquinol, when mixed with copper (Fig. 1), killed two types of prostate cancer cell in Petri dishes. The drug without copper also slowed the growth of prostate tumors implanted in mice by up to two-thirds, apparently by soaking up copper ions (charged atoms) present in the implanted tumor cells.

Prostate cancer struck approximately 219,000 U.S. men in 2007 and killed some 27,000 of them, according to National Cancer Institute estimates.

Many types of cancer typically show high levels of copper, including tumors of the prostate, breast, colon, lung, and …

Collagens—we might take them for granted, but without them there would be no way to build tissues of the heart, skin, cornea, or bones. In much the same way that wood is used to frame a house and form a structure for the overlying construction materials, collagens are proteins used in the framing of mammalian tissues, but gaining an accurate picture of their three-dimensional structure in the body has proven more difficult. Knowing more about the structure of collagens could help biochemists improve their understanding of heart disease and cancer. Thanks to work by a research …

Any time we move our arms, billions of protein molecules work in unison to contract one muscle while letting another muscle relax. The mechanical details of muscle contraction have been known for a long time, deduced from experiments with frog legs, reconstruction of the proteins involved in crystallographic studies, and many other kinds of research. But no one has ever taken such detailed time-lapse molecular pictures of the proteins at work within living muscle. Researchers from Brandeis University, the University of Florence, and Illinois Institute of Technology investigated whether the muscle-contracting proteins work the same way inside muscles as they do inside laboratories. But muscle cells are full of water and the proteins don’t line up quite as regularly as they would purified in crystals. So rather than spend 30 to 40 hours collecting data with a typical x-ray tube, the researchers turned to the BioCAT beamline 18-ID at the APS. With a million times more intensity than a “home source” x-ray tube—and the ability to focus the x-ray beam into a narrow line—the team got a detailed view of the proteins …

You are what you eat” is just another way of saying that input determines output, after some metabolic messing around in between. It’s the “in between” that interests biologists, because that is where the difference between healthy and diseased cells can originate. If the normal sequence of intermediate steps between the beginning and end of a biochemical pathway is disrupted, the disruption can lead to major changes in cellular functioning. A better understanding of the input-output relationships is critical to medical progress. The steps necessary for producing the right output can be numerous and complex, and some pathways have taken decades to unravel. In one of the identified mechanisms, called “two-component signal transduction,” the input causes a receiver domain to be phosphorylated, a step that governs what happens to the output modules. By employing x-ray scattering and electron microscopy researchers from Pennsylvania State University; the University of California, Berkeley; Lawrence Berkeley National Laboratory; The University of Georgia; and the Illinois Institute of Technology using the BioCAT 18-ID beamline at the APS were able to describe—in stunning detail—a novel two-component mechanism for assembling a protein associated with bacterial transcription. Their work greatly advances our understanding of what …

Michael Reedy (Duke University) and Tanya Bekyarova (Illinois Institute of Technology) are shown in action on the BioCAT beam line 18-ID at the U.S. Department of Energy’s Advanced Photon Source (APS), Argonne National Laboratory. They are studying mechanisms of stretch activation in insect flight muscle.

Stretch activation is very important in human heart muscle when contraction of one part of the heart stretches adjacent muscle tissue causing it to respond a moment later by generating more force. This action aids cardiac “ejection,” i.e., the amount of blood pumped per beat. Muscle structure and function can be studied using high-brilliance x-ray beams, such as those produced by the APS, and the experimental technique time-resolved small-angle fiber diffraction.

Unfortunately, cardiac muscle is relatively poorly ordered and the diffraction patterns relatively uninformative. Fortunately, because of its physiological properties, the flight muscle of insects can be a good model system for cardiac muscle. And because of its high degree of structural order, insect flight muscle produces rich and informative (not to say beautiful) diffraction patterns (image lower right). Muscle contracts by the cyclical action of motor proteins called “myosin” that bind to particular sites on another protein called “actin.” This …

Collagen is the main (and most abundant) protein in all mammalian connective tissues, including those of the heart, lungs, skin, and tendons. It is also the primary protein in bones and teeth. Bodily malfunctions involving this protein can lead to heart disease and cancer. We know a good deal about how collagen is produced in the body, how it regenerates, and about its physiological structure. But because the collagen protein is so large and insoluble, solving its three-dimensional molecular structure has long been regarded as an impossible, but important, problem. Now, innovative synchrotron x-ray research techniques have yielded new information on the molecular structure of collagen. Because this ubiquitous protein is involved in cancer and heart disease, the data obtained in this study may help in the fight against these deadly ailments.

By adapting methods commonly used for studying much smaller and simpler proteins, researchers from the Illinois Institute of Technology, the Rosalind Franklin University of Medicine and Science, the University of Stirling, and Cardiff University, using the BioCAT, SBC-CAT, and SER-CAT beamlines at the APS, have successfully determined the molecular structure of collagen while it is still intact and undisturbed within whole tendons removed from rat tails …