Science Concentrates

Protein stabilizes -hemoglobin

Researchers have determined how a major component of hemoglobin--the protein complex that carries oxygen to tissues and organs--retains its structure and stability. In the body, hemoglobin is assembled from - and -hemoglobin subunits. Although -hemoglobin is relatively stable, -hemoglobin is not. In fact, -hemoglobin can unfold and release heme, leading to serious blood disorders. Thus, it's necessary to stabilize -hemoglobin before it is incorporated into hemoglobin. This function is filled by -hemoglobin-stabilizing protein (AHSP). Princeton University molecular biologist Yigong Shi and his colleagues have now obtained a crystal structure of the -hemoglobin/AHSP complex (shown) that reveals how the protein stabilizes -hemoglobin (Nature 2005, 435, 697). The researchers report that binding to AHSP causes a-hemoglobin to "undergo drastic structural rearrangements." As a result, the heme iron (large red ball) assumes a nonreactive ferric form in which it is coordinated by two histidines of -hemoglobin, in addition to the four nitrogen atoms on heme's porphyrin ring.

Endocrine disrupters' effects are inheritable

Exposure to two commonly used pesticides and fungicides during gestation can cause developmental defects in male fertility that are transmitted to subsequent generations through the male line, according to a new study (Science 2005, 308, 1466). Michael K. Skinner and coworkers at Washington State University exposed pregnant rats to the fu ngicide vinclozolin (shown) and the pesticide methoxychlor. More than 90% of the male offspring in the first four generations of the groups treated with the chemicals demonstrated a decrease in fertility, including about 10% that were completely infertile. The most likely cause is a change in the methylation pattern of the genes rather than a mutation in the DNA sequence. This study marks the first time that such "transgenerational" effects of endocrine disrupters have been documented, Skinner says.

Chemical steps to biomass fuel

Integrated biorefineries have been proposed as a way to make gasoline, diesel fuel, and chemical feedstocks directly from carbohydrates such as sugars, starch, and cellulose derived from dedicated crops, agricultural waste, and urban yard debris. Chemical engineers George W. Huber, James A. Dumesic, and coworkers at the University of Wisconsin, Madison, who have been developing lab-scale chemical processes that could be important in biorefineries, now report chemistry to produce C₇ to C₁₅ alkanes from biomass (Science 2005, 308, 1446). The team designed a multistep aqueous-phase process that begins with carbonyl-containing intermediates, such as hydroxymethylfurfural, that can be made from glucose. The intermediates first undergo an aldol cross-condensation with acetone or an aldol self-condensation using a solid base catalyst to make larger compounds, followed by a dehydration-hydrogenation process that uses a bifunctional metal-acid catalyst to form the linear alkanes. The alkanes can be phase-separated from the water. Biorefinery production of alkanes to make sulfur-free gasoline and diesel could be more energy-efficient and less costly than producing ethanol or hydrogen from biomass.

Toxic exposure may reprogram gene response

A new study indicates that exposure to certain toxic chemicals during early, critical developmental periods may change the way certain genes respond to the female hormone estrogen (Proc. Natl. Acad. Sci. USA, published online, www.pnas.org/papbyrecent.shtml). This genetic reprogramming may determine whether people who are genetically susceptible to a disease actually develop the disease, says lead author Cheryl L. Walker at the University of Texas M. D. Anderson Cancer Center. Walker and her colleagues used rats with a genetic defect that makes them susceptible to benign uterine tumors. The rats were exposed to the synthetic estrogen diethylstilbestrol (DES) when they were three to five days old--a critical period of uterine development for rats that corresponds to the first trimester of human fetal development. When the DES-treated rats reached adulthood, 92% developed uterine tumors, but only 65% of the control rats developed tumors. "We found that the DES treatment somehow 'reprogrammed' how these genes respond to estrogen, making them hypersensitive to the effects of the hormone," Walker says. For humans, this research may imply that early exposures may be important "in determining who develops hormone-dependent tumors as an adult," she explains.

Prion disease requires cell attachment

Infectious prions have been found incapable of causing the prion disease scrapie if an animal's prion protein cannot attach to cell membranes (Science 2005, 308, 1435). Most endogenous prion protein is expressed with a sugar-lipid appendage that permits attachment to cell surfaces. Bruce W. Chesebro of the National Institute of Allergy & Infectious Diseases' Rocky Mountain Laboratories, Hamilton, Mont., and coworkers find that mice engineered to express prion protein that can't attach to cells don't develop scrapie when exposed to an infectious agent. However, they do develop Alzheimer's-like plaques, indicating that prion protein misfolding does not require membrane attachment. Adriano Aguzzi of University Hospital of Zurich comments, "It is almost unavoidable to conclude that prion replication avails itself of membrane-bound signal transducers to elicit brain damage."