Single-base pair unwinding and asynchronous RNA release by the hepatitis C virus NS3 helicase     

Cheng W  Arunajadai SG  Moffitt JR  Tinoco I  Bustamante C 《Science (New York, N.Y.)》2011,333(6050):1746-1749

Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in double-stranded nucleic acids (dsNAs). Studies have suggested that these helicases unzip dsNAs in single-base pair increments, consuming one ATP molecule per base pair, but direct evidence for this mechanism is lacking. We used optical tweezers to follow the unwinding of double-stranded RNA by the hepatitis C virus NS3 helicase. Single-base pair steps by NS3 were observed, along with nascent nucleotide release that was asynchronous with base pair opening. Asynchronous release of nascent nucleotides rationalizes various observations of its dsNA unwinding and may be used to coordinate the translocation speed of NS3 along the RNA during viral replication.  相似文献   

A single IGF1 allele is a major determinant of small size in dogs   总被引：3，自引：0，他引：3  

Sutter NB  Bustamante CD  Chase K  Gray MM  Zhao K  Zhu L  Padhukasahasram B  Karlins E  Davis S  Jones PG  Quignon P  Johnson GS  Parker HG  Fretwell N  Mosher DS  Lawler DF  Satyaraj E  Nordborg M  Lark KG  Wayne RK  Ostrander EA 《Science (New York, N.Y.)》2007,316(5821):112-115

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.  相似文献   

Flexible control of mutual inhibition: a neural model of two-interval discrimination     

Machens CK  Romo R  Brody CD 《Science (New York, N.Y.)》2005,307(5712):1121-1124

Networks adapt to environmental demands by switching between distinct dynamical behaviors. The activity of frontal-lobe neurons during two-interval discrimination tasks is an example of these adaptable dynamics. Subjects first perceive a stimulus, then hold it in working memory, and finally make a decision by comparing it with a second stimulus. We present a simple mutual-inhibition network model that captures all three task phases within a single framework. The model integrates both working memory and decision making because its dynamical properties are easily controlled without changing its connectivity. Mutual inhibition between nonlinear units is a useful design motif for networks that must display multiple behaviors.  相似文献   

Regulation of bone mass in mice by the lipoxygenase gene Alox15     

Klein RF  Allard J  Avnur Z  Nikolcheva T  Rotstein D  Carlos AS  Shea M  Waters RV  Belknap JK  Peltz G  Orwoll ES 《Science (New York, N.Y.)》2004,303(5655):229-232

The development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development. Pharmacologic inhibitors of this enzyme improved bone density and strength in two rodent models of osteoporosis. These results suggest that drugs targeting the 12/15-lipoxygenase pathway merit investigation as a therapy for osteoporosis.  相似文献   

Ecology. Rapid domestication of marine species     

Duarte CM  Marbá N  Holmer M 《Science (New York, N.Y.)》2007,316(5823):382-383

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A host-targeting signal in virulence proteins reveals a secretome in malarial infection     

Hiller NL  Bhattacharjee S  van Ooij C  Liolios K  Harrison T  Lopez-Estraño C  Haldar K 《Science (New York, N.Y.)》2004,306(5703):1934-1937

Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11-amino acid signal required for the secretion of proteins from the Plasmodium falciparum vacuole to the human erythrocyte. Bioinformatics predicted a secretome of >320 proteins and conservation of the signal across parasite species. Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter. Erythrocyte modification by the parasite may involve plasmodial heat shock proteins and be vastly more complex than hitherto realized.  相似文献   

Sequence-directed DNA translocation by purified FtsK     

Pease PJ  Levy O  Cost GJ  Gore J  Ptacin JL  Sherratt D  Bustamante C  Cozzarelli NR 《Science (New York, N.Y.)》2005,307(5709):586-590

DNA translocases are molecular motors that move rapidly along DNA using adenosine triphosphate as the source of energy. We directly observed the movement of purified FtsK, an Escherichia coli translocase, on single DNA molecules. The protein moves at 5 kilobases per second and against forces up to 60 piconewtons, and locally reverses direction without dissociation. On three natural substrates, independent of its initial binding position, FtsK efficiently translocates over long distances to the terminal region of the E. coli chromosome, as it does in vivo. Our results imply that FtsK is a bidirectional motor that changes direction in response to short, asymmetric directing DNA sequences.  相似文献   

Closed-shell molecules that ionize more readily than cesium     

Cotton FA  Gruhn NE  Gu J  Huang P  Lichtenberger DL  Murillo CA  Van Dorn LO  Wilkinson CC 《Science (New York, N.Y.)》2002,298(5600):1971-1974

We report a class of molecules with extremely low ionization enthalpies, one member of which has been determined to have a gas-phase ionization energy (onset, 3.51 electron volts) lower than that of the cesium atom (which has the lowest gas-phase ionization energy of the elements) or of any other known closed-shell molecule or neutral transient species reported. The molecules are dimetal complexes with the general formula M2(hpp)4 (where M is Cr, Mo, or W, and hpp is the anion of 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine), structurally characterized in the solid state, spectroscopically characterized in the gas phase, and modeled with theoretical computations. The low-energy ionization of each molecule corresponds to the removal of an electron from the delta bonding orbital of the quadruple metal-metal bond, and a strong interaction of this orbital with a filled orbital on the hpp ligands largely accounts for the low ionization energies.  相似文献   

Sequential establishment of stripe patterns in an expanding cell population     

Liu C  Fu X  Liu L  Ren X  Chau CK  Li S  Xiang L  Zeng H  Chen G  Tang LH  Lenz P  Cui X  Huang W  Hwa T  Huang JD 《Science (New York, N.Y.)》2011,334(6053):238-241

Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.  相似文献   

Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins   总被引：3，自引：0，他引：3  

Zhou D  Cantu C  Sagiv Y  Schrantz N  Kulkarni AB  Qi X  Mahuran DJ  Morales CR  Grabowski GA  Benlagha K  Savage P  Bendelac A  Teyton L 《Science (New York, N.Y.)》2004,303(5657):523-527

It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Valpha14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the loading as well as the editing of lipids on CD1. Transient complexes between CD1, lipid, and LTP suggested a "tug-of-war" model in which lipid exchange between CD1 and LTP is on the basis of their respective affinities for lipids. LTPs constitute a previously unknown link between lipid metabolism and immunity and are likely to exert a profound influence on the repertoire of self, tumor, and microbial lipid antigens.  相似文献