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Researchers at Yale University have obtained the clearest picture to date of tau protein’s solution-phase structure (J. Am. Chem. Soc., DOI: 10.1021/ja305206m). Tau, a macromolecule that aggregates and forms fibrils inside the neurons of Alzheimer’s patients, has been structurally investigated before. But now, using single-molecule fluorescence resonance energy transfer (FRET), Shana Elbaum-Garfinkle and Elizabeth Rhoades have made measurements on individual tau proteins rather than on large ensembles of them. Not only has the approach yielded a more detailed model of the native tau structure, says Jeff Kuret, a biochemist at Ohio State University, it has also provided “new insight into the conformational changes that likely precede tau aggregation.” That’s because Elbaum-Garfinkle and Rhoades also mapped tau’s structure when the protein was bound to heparin, a polyanion known to induce formation of tau aggregates. The researchers observed that in the presence of heparin, tau’s end segments sever long-range contact with one another and that one of the protein’s inner segments, called the microtubule-binding region, compresses. Designing drugs to stabilize tau and prevent these structural changesmightbeonedisease-fightingstrategy, the researchers suggest.—LKW
A distorted hydrogen bond shapes how a bacterial protein distinguishes essential phosphate from toxic arsenate, researchers report (Nature, DOI: 10.1038/nature11517). The work represents another nail in the coffin for the controversial claim that a microbe called GFAJ-1 can incorporate arsenate in its metabolites. Wondering how life evolved to deal with arsenate-rich environments, Weizmann Institute of Science postdoc Mikael Elias, Dan S. Tawfik, and colleagues turned to periplasmic phosphate-binding proteins, which regulate passage of phosphate anions through microbes’ inner membranes. They now find that versions When binding of this protein from several bacteria, including to arsenate (at GFAJ-1, are highly selective for phosphate. bottom), a X-ray structures of the protein, from the key hydrogen bond in P. bacterium Pseudomonas fluorescens, reveal fluorescens that when arsenate binds, a hydrogen bond to an periplasmic aspartic acid residue becomes distorted. Mutating phosphate-binding the residue makes the protein less choosy for phosprotein deviates from the 180° norm (at top). phate over arsenate, reinforcing the idea that the distortion drives the protein’s phosphate selectivity. Tawfik thinks that mechanism is also at play in the analogous protein from GFAJ-1, allowing it to survive in arsenate-rich environments. Scripps Research Institute biochemist Gerald F. Joyce says GFAJ-1 likely has multiple adaptations: “Now can we all stop talking about ‘arsenic-based life’?”—CD trodes, the devices are entirely metal-free. Because it’s easy to transfer graphene to various substrates, the researchers fabricated some devices on flexible plastic. Those units showed no memory degradation upon bending. The team also constructed memory devices on glass, a popular material for handheld electronics. Tour points out that because glass is a popular building material, the devices could add embedded memory to smart glass. Considering silicon oxide’s popularity in the semiconductor industry and graphene’s promise as a transparent electrode material, the researchers think the new memory system has a future in transparent materials in terms of composition and processing.—BH
SEE-THROUGH MEMORY DEVICES By marrying silicon oxide and graphene, researchers have developed transparent memory devices that could find use in flexible electronics and sophisticated displays (Nat. Commun., DOI: 10.1038/ ncomms2110). The work comes from a Rice University team led by Douglas Natelson and James M. Tour. Silicon oxide, with its recently discovered resistive switching properties, serves as the information storage material. Graphene makes up the device’s electrodes. With the exception of the leads that attach to the graphene elecRICE U
A transparent, flexible memory device.
BACTERIA CONFISCATE UNSTABLE IRONCITRATE COMPLEX A unique bacterial protein selectively binds an unstable triferric citrate complex to import iron into Bacillus cereus
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cells, reports a team from the University of California, Berkeley (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1210131109). Iron is an essential element that bacteria commonly sequester by sending ligands, called siderophores, to chelate insoluble Fe3+ in the environment. Selective binding and transport proteins then convey the complexes back into the cells. Common siderophores include citrate ([COH(COO)(CH2COO)2]3–) and citratebased ligands. Citrate’s carboxyl and hydroxyl groups coordinate Fe3+. Previously, however, citrate-binding proteins were observed harboring only Fe(citrate)2 and Fe2(citrate)2. Kenneth N. Raymond and colleagues have now identified a B. cereus protein, christened ferric citrate-binding protein C, or FctC, that selectively binds Fe3(citrate)3 even when other iron-citrate species are present in solution. Only a few closely related species have genes for similar proteins, so FctC may give the B. cereus group an advantage by enabling import of iron complexes that other bacteria cannot sequester.—JK
NATURE
BACTERIAL PROTEIN OUTWITS ARSENATE
A DETAILED LOOK AT TAU
J. AM. CHEM. SOC.
Scientists have developed a method for synthesizing polysaccharides with units linked by amide groups instead of ethers, giving researchers a new tool to generate well-defined mimics of these key biomacromolecules (J. Am. Chem. Soc., DOI: 10.1021/ja305900r). Boston University’s Mark W. Grinstaff and Eric L. Dane produced the polyamidosaccharides via an anionic ring-opening polymerization of a strained β-lactam prepared from d-glucal, a glucose derivative. Like other large biomolecules, such as nucleic acids and peptides, polysaccharides play innumerable roles in biology and technology. For example, the sulfated A computer simulation polysaccharide heparin predicts the is used as an anticoagustructure of a lant, and protein-bound polysaccharide polysaccharides are used that substitutes in cancer therapy. Yet an amide for their synthesis has proved ether linkages.
challenging. The new polysaccharides show promise as natural polysaccharide mimics, Grinstaff says, noting that they bind the lectin concanavalin A at the same site that natural polysaccharides bind. Grinstaff hopes the method will allow polysaccharide research to blossom in the same manner as research on other biomolecules. “I would like to think that we have the same opportunity here with further development,” he says.—EKW
problems, including cancer, diabetes, and childhood obesity. In a 3-D modeling study, Michael E. Baker and Charlie Chandsawangbhuwana of the University of California, San Diego, found that a BPA metabolite known as MBP, which has three more carbon atoms between the Structural phenol rings than does models show how MBP is BPA, fits better into shaped more estrogen receptors than like estradiol BPA itself. Previous and binds better studies have found that to estrogen receptors than MBP binds 1,000 times more strongly than BPA. BPA; BPA is But the structural basis too short for optimal binding. for the higher affinity hasn’tbeendetermined. The UCSD researchers discovered that MBP’s longer structure allows both ends of the molecule to interact with amino acids in the receptors, just like estradiol does. Because it is shorter, BPA contacts the receptors only at one end. MBP levels in people should be monitored for possible health concerns, Baker says. He also suggests MBP could be used as a template to develop drugs that bind estrogen receptors to treat conditions linked to abnormal estrogen activity, such as breast and prostate cancers.—SR
NANOPARTICLE MIDDLEMEN TRIGGER DRUG RELEASE
RED FLAG RAISED FOR BPA METABOLITE A molecular modeling study suggests that the controversial polycarbonate plastic building block bisphenol A may be less problematic as an endocrine-disrupting compound than one of its metabolites (PLoS One, DOI: 10.1371/journal.pone.0046078). BPA structurally resembles estradiol and binds weakly to estrogen receptors. Thus, BPA is thought to disrupt estrogen signaling and has been associated with health
A hydrogel containing lanthanide-based nanoparticles releases proteins inside the gel when hit with near-infrared light (J. Am. Chem. Soc., DOI: 10.1021/ ja308876j). The nanoparticlestudded gel could enable doctors to cue the release of protein drugs deep inside a patient’s tissues, the developers say. Yue Zhao of the University of Sherbrooke, in Quebec, and Neil R. Branda of Simon Fraser University, in British Columbia, wanted to make hydrogels responsive to near-IR light, which is safer and can penetrate deeper into tissue than ultraviolet light. They impregnated a hydrogel with nanoparticles composed of a NaYF4 core doped with thulium and ytterbium and wrapped with a NaYF4 shell. The hydrogel is a cross-linked
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web of polyacrylamide and polyethylene glycol, held together by photoresponsive o-nitrobenzyl groups. When exposed to near-IR light, the nanoparticles emit UV light through a process called upconversion. The UV light then triggers the nitrobenzyl groups to cleave the polymer chains. The team tested their gel by filling it with a fluorescently labeled protein. After about 50 minutes of irradiation with near-IR light, almost 70% of the protein escaped from the gel.—EKW
BROCCOLI CAN SILENCE BACTERIA Research shows that natural isothiocyanates in broccoli can stop the chemical communication of Pseudomonas aeruginosa, which is implicated in cystic fibrosis and AIDS complications. Many microbes rely on this communication, called quorum sensing, to form biofilms or activate virulence. As antibiotic resistance rises in pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa, researchers are increasingly interested in combating bacterial pathogens by interfering with their chemical communication. Scientists at Ben-Gurion University of the Negev, in Israel, led by chemical biologist Michael M. Meijler found that Broccoli two broccoli isothiocyaplants make nates—sulforaphane and molecules, erucin—interfere with such as sulforaphane, P. aeruginosa chitchat by binding to important that stop proteins involved in the bacterial conversations. communication machinery (MedChemComm, DOI: 10.1039/c2md20196h). Sulforaphane and erucin join a toolbox of bacterial conversation stoppers that may one day be used to fight pathogens. This is not the first time sulfurrichcompoundshavebeenfound to interfere with quorum sensing. Isothiocyanates and disulfides from horseradish and garlic have also been shown to block bacterial conversations. Meij ler’s team notes that P. aeruginosa is not a common broccoli pathogen, but the related bacterium P. fluorescens is. —SE
SHUTTERSTOCK
AMIDE-LINKED POLYSACCHARIDES
UCSD SCHO O L O F M EDICIN E
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