SCIENCE & TECHNOLOGY CONCENTRATESSPINNING IMPROVESNMR OF LARGE PROTEINSA protein solution continuously spun in arotor produces a sediment that yields highqualitynuclear magnetic resonance data,providing a new means to determine structuresof large proteins, reports a researchgroup led by Ivano Bertini and ClaudioLuchinat of the University of Florence,in Italy ( Proc. Natl. Acad. Sci. USA, DOI:10.1073/pnas.1103854108). The approachmelds protein ultracentrifugation, a commonprotein purification technique, withmagic-angle spinning, an NMR methodused to get structural information aboutamorphous solids. The team demonstratedthe combination using an iron-free formof the iron-storage protein ferritin, whichconsists of 24 subunits and has a mass of480 kilodaltons. Data from ultracentrifugedprotein solutions match those fromcrystalline protein samples in both oneandtwo-dimensional experiments, theresearchers show. The ultracentrifugationapproach should facilitate study of proteinsthat are too large for typical solutionNMR, they say. It will also enable experimentsthat are difficult to do with crystals,such as titrations with reagents. —JKURSOLIC ACID MIGHTKEEP THE DOCTOR AWAYA polycyclic natural product called ursolicacid that’s found in large amounts in applepeels might be just what the doctor shouldorder to treat age- and disease-relatedmuscle atrophy, according to a Universityof Iowa study ( Cell Metab., DOI: 10.1016/j.cmet.<strong>20</strong>11.03.0<strong>20</strong>). A team led by ChristopherM. Adams monitored gene activity inthe muscles of people and mice that werefasting in order to study muscle weakening.The researchers then comparedmRNA expression signatures with theresponse of cells to some 1,300 bioactivemolecules. They singled out ursolic acidas a lone inhibitor of atrophy-associatedgene expression. The researchers nextgave ursolic acid to mice and observedthat it helps protect fasting mice againstmuscle weakening and helps mice with anormal diet grow muscle. The mice alsobecame leaner and had lower blood levelsof glucose, cholesterol, and triglycerides.It seems the adage “an apple a day keepsthe doctor away” might have real therapeuticmerit, Adams says. —SRMARKING SUGAR’S SPOTBy using X-ray crystallography, researchers have learned how a sugartransferringenzyme recognizes peptide sequences that trigger a commonprotein modification reaction—asparagine-linked glycosylation(Nature, DOI: 10.1038/nature10151).Saccharide attachment at asparagine’sside-chain nitrogen is important for proteinfolding, cell-cell communication, andmore, but researchers know little aboutthe attachment process. It requires eithera serine or threonine to be two residuesaway from the asparagine to be modified,but it’s not clear how asparagine’s nitrogen,a poor nucleophile, gets activatedfor modification. To answer that question,Kaspar P. Locher, Christian Lizak, and coworkersat ETH Zurich crystallized a bacterialtransferase together with a peptidesubstrate. They found that the hydroxylcontainingamino acid helps the enzymerecognize the substrate, but it doesn’tFAST, SENSITIVEDNA SEQUENCINGFluorogenic pyrosequencing, a new DNAsequencing method, combines the speedand one-color detection of conventionalpyrosequencing with the sensitivityof fluorescence-based methods ( Nat.Methods, DOI: 10.1038/nmeth.1629). Inthe new method, as in other sequencingby-synthesismethods, the sequence ofa target DNA molecule is determined byidentifying the order in which nucleotidesare incorporated when that DNAis used as a template for DNA synthesis.X. Sunney Xie and coworkers at HarvardUniversity label all four nucleotides withan identical dye, which is nonfluorescentwhen it is attached to a nucleotide. Addinga nucleotide to the growing DNA strandreleases the dye, which becomes fluorescent.The dye is trapped in polymeric microreactors,in which the DNA is tethered.The fluorescence is detected and the dyeis washed away. Repeating the cycle manytimes with each of the four nucleotidesreveals the sequence of the DNA template.Xie and coworkers believe the method willoffer low cost, high throughput, and rapidturnaround.—CHAHydrogen bonding to anionic aminoacids (green) from an enzyme(blue) readies a peptide substrate’sasparagine (red) for sugar transfer.The metal ion (pink) is manganeseor magnesium.facilitate the reaction. That job belongs to an aspartate and a glutamate inthe transferase, which juice up the asparagine by forming hydrogen bondsto its amide protons. The team says more structures need to be solved tofully understand the reaction. —CDOPTICAL IMAGING OFLIGAND-PROTEIN BINDINGA new technique called PHOTON (photostableoptical nanoscopy) achieves sufficientlyfine resolution to enable detailedoptical spectroscopic imaging of ligandbindingsites on individual protein molecules( Nanoscale, DOI: 10.1039/c1nr10182j).Such sites can be imaged crystallographically,but this requires that the proteinfirst be crystallized, and crystallographyis incapable of following binding kineticsand real-time conformational changes.PHOTON, developed by Tao Huang andXiao-Hong Nancy Xu of Old DominionUniversity, uses an optical microscope toanalyze scattered light by single-moleculesilver nanoparticle optical biosensors.The technique achieves 1.2-nm spatial and100-millisecond time resolution, comparedwith <strong>20</strong>-nm spatial and minute tohour time resolution previously. Huangand Xu use PHOTON to image single biotinmolecules and their binding sites on theprotein streptavidin. The technique doesnot cause fluorescence, decomposition, ortoxicity in living cells, making it possible tostudy living microorganisms for extendedperiods of time, Xu notes. —SBCOURTESY OF KASPAR LOCHERWWW.CEN-ONLINE.ORG 32 JUNE <strong>20</strong>, <strong>20</strong>11
SCIENCE & TECHNOLOGYMITCH JACOBY/C&ENTHERMOELECTRICSMAKE A COMEBACKNew concepts and materials invigorate acommercially active but obscure field specializingin HEATING, COOLING, AND POWER GENERATIONMITCH JACOBY , C&EN CHICAGO“TEN OR 15 YEARS AGO, nobody wantedto hear about thermoelectrics. Back then,people couldn’t even spell the word.”With playful exaggeration, MercouriG. Kanatzidis, a Northwestern Universitychemistry professor and materials specialist,makes the point that during the past decade,the field of thermoelectrics—whichencompasses a collection of heating, cooling,and power generation technologiesenabled by a unique class of semiconductors—isundergoing a renaissance.In the early 1960s, long after the curiouscollection of properties that definethermoelectric materials was discovered,manufacturers began producing specialtycooling and power-supply devices largelybased on the thermoelectric properties ofbismuth telluride, Bi 2 Te 3 . This niche market,which mainly served the military andaerospace industry, didn’t disappear, butthe next 30-plus years witnessed a steepdrop in interest in the topic.“In the mid-1990s, universities rarelytaught thermoelectrics in physics courses,”Kanatzidis points out. He adds, “It was aforgotten concept. Now it’s finally comingof age.”After years of sitting mostly unnoticedin a quiet corner of science, thermoelectricsis again drawing attention. In additionto supplying temperature managementand power products to the military andaerospace industry—for example as miniaturecoolers that chill the infrared detectorscentral to the imaging electronics inheat-seeking missiles and night-vision systems—thefew manufacturers in this areanow make millions of units each year fordown-to-earth civilian use. Their productsare found in climate-control automobileseats offered by major automakers, thermalcyclers for polymerase chain reactionsystems, and power generators for applicationsfar from an electrical grid.At the same time, researchers in industryand academia, motivated by recent fundamentalmaterials advances, are focusingtheir synthesis, analytical, and engineeringskills on discovering new thermoelectricmaterials and designing new ways to usethem. They hope these advances willprovide enhanced thermoelectric performanceand lead to a broader range ofproducts. Despite key advantages of thermoelectricpower and cooling systems relativeto conventional ones—for example,they have no moving parts, making themmechanically simpler, and they do not emitgreenhouse gases or depend on environmentallyharmful coolant fluids—only anarrow range of thermoelectric productsSHOP TALK Methodsto synthesize newthermoelectricsolids (samplein test tube) andanalyze them viaX-ray diffraction andother techniquesare key aspects ofresearch conductedby Northwestern’sKanatzidis (in vest)and coworkers.has been commercialized.One of thefield’s much talkedabout goals is tomake thermoelectricdevices thatwork well at hightemperature andcan generate electricitycost-effectivelyfrom wasteheat recovered, forexample, from industrialplants or automobile exhaust.The key observations that underpin thethermoelectric effect were made way backin the early 1800s. In 1821, German physicistThomas Johann Seebeck discoveredthat if a loop made from dissimilar metalsis exposed to a temperature gradient (oneside of the loop warm, the other cool) theloop can deflect a nearby compass needle.That set of conditions generates an electricalcurrent and a magnetic field.Another key observation was madeby French physicist Jean-Charles Peltierin 1834. Peltier found that if a current isapplied across a junction of dissimilarelectrically conductive materials, the junctioncan heat up or cool down. Reversingthe current flow, by switching the batteryhookups, for example, results in the oppositeheating or cooling effect.IN MOST MATERIALS, the properties thatcause a temperature change as a result ofan applied current are too weak to be usefulfor thermoelectric applications. The sameis true for those that generate an electricalcurrent in response to a temperaturegradient.In fact, materials that exhibit a pronouncedthermoelectric effect are ratherexotic, according to Lon E. Bell. Bell foundedthermoelectrics manufacturer Amerigon,based in Northville, Mich., and laterthe wholly owned thermoelectrics subsidiary,BSST, in Irwindale, Calif. For materialsto be useful thermoelectrically, he explains,they need to be good electrical conductorsand, at the same time, poor thermalconductors. They also must prominentlydisplay the effect observed by Seebeck.One of the challenges in finding usefulmaterials is that the desired qualities areinterrelated via the substance’s electronicproperties: Improvement in one propertyoften comes at the expense of another.In these materials, electrons serve as the“working fluid,” just as liquid refrigerantsWWW.CEN-ONLINE.ORG 33 JUNE <strong>20</strong>, <strong>20</strong>11