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A phase diagram for jammed matter

Chaoming Song — 2008-05-29T14:31:12-00:00

Nature, Vol. 453, No. 7195., pp. 629-632.

Kemp elimination catalysts by computational enzyme design

Daniela Röthlisberger — 2008-03-21T04:33:18-00:00

Nature (19 March 2008)

Dynamic binding orientations direct activity of HIV reverse transcriptase

Elio Abbondanzieri — 2008-05-08T07:42:20-00:00

Nature, Vol. 453, No. 7192. (May 2008), pp. 184-189.

Modeling transient collapsed states of an unfolded protein to provide insights into early folding events

Daniel Felitsky — 2008-05-07T07:23:14-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 17. (29 April 2008), pp. 6278-6283.

The primary driving force for protein folding is the sequestration of hydrophobic side chains from solvent water, but the means whereby the amino acid sequence directs the folding process to form the correct final folded state is not well understood. Measurements of NMR line broadening in spin-labeled samples of unfolded apomyoglobin at pH 2.3 have been used to derive a quantitative model for transient hydrophobic interactions between various sites in the polypeptide chain, as would occur during the initiation of protein folding. Local clusters of residues with high values for the parameter "average area buried upon folding" (AABUF) form foci not only for local contacts but for long-range interactions, the relative frequencies of which can be understood in terms of differences in the extent of reduction in chain configurational entropy that occurs upon formation of nonlocal contacts. These results complement the striking correlation previously observed between the kinetic folding process of apomyoglobin and the AABUF of its amino acid sequence [Nishimura C, Lietzow MA, Dyson HJ, Wright PE (2005) J Mol Biol 351:383-392]. For the acid-unfolded states of apomyoglobin, our approach identifies multiple distinct hydrophobic clusters of differing thermodynamic stability. The most structured of these clusters, although sparsely populated, have both native-like and nonnative character; the specificity of the transient long-range contacts observed in these states suggests that they play a key role in initiating chain collapse and folding. 10.1073/pnas.0710641105

The thermal impulse response of Escherichia coli

Eli Paster — 2008-05-02T10:19:05-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 14. (8 April 2008), pp. 5373-5377.

Swimming Escherichia coli responds to changes in temperature by modifying its motor behavior. Previous studies using populations of cells have shown that E. coli accumulate in spatial thermal gradients, but these experiments did not cleanly separate thermal responses from chemotactic responses. Here we have isolated the thermal response by studying the behavior of single, tethered cells. The motor output of cells grown at 33degreesC was measured at constant temperature, from 10degrees to 40degreesC, and in response to small, impulsive increases in temperature, from 23degrees to 43degreesC. The thermal impulse response at temperatures < 31degreesC is similar to the chemotactic impulse response: Both follow a similar time course, share the same directionality, and show biphasic characteristics. At temperatures > 31degreesC, some cells show an inverted response, switching from warm- to cold-seeking behavior. The fraction of inverted responses increases nonlinearly with temperature, switching steeply at the preferred temperature of 37degreesC. 10.1073/pnas.0709903105

Evolvability and hierarchy in rewired bacterial gene networks

Mark Isalan — 2008-04-16T19:45:06-00:00

Nature, Vol. 452, No. 7189. (17 April 2008), pp. 840-845.

Following translation by single ribosomes one codon at a time

Jin-Der Wen — 2008-03-10T16:18:13-00:00

Nature (09 March 2008)

Watching rocks grow

Veysey — 2008-04-02T09:32:48-00:00

Nat Phys, Vol. 4, No. 4. (April 2008), pp. 310-313.

Differential Regulation of Dynein and Kinesin Motor Proteins by Tau

Ram Dixit — 2008-01-20T05:11:55-00:00

Science (17 January 2008), 1152993.

Dynein and kinesin motor proteins transport cellular cargos toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein and kinesin motility, we conducted single molecule studies of motor proteins moving along tau-decorated microtubules. Dynein tended to reverse direction whereas kinesin tended to detach at patches of bound tau. Kinesin was inhibited at ~10-fold lower tau concentration than dynein and the microtubule-binding domain of tau was sufficient to inhibit motor activity. The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport. 10.1126/science.1152993

Cooperative folding kinetics of BBL protein and peripheral subunit-binding domain homologues

Wookyung Yu — 2008-02-22T09:40:43-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 7. (19 February 2008), pp. 2397-2402.

Recent experiments claiming that Naf-BBL protein follows a global downhill folding raised an important controversy as to the folding mechanism of fast-folding proteins. Under the global downhill folding scenario, not only do proteins undergo a gradual folding, but folding events along the continuous folding pathway also could be mapped out from the equilibrium denaturation experiment. Based on the exact calculation using a free energy landscape, relaxation eigenmodes from a master equation, and Monte Carlo simulation of an extended MunozEaton model that incorporates multiscale-heterogeneous pairwise interactions between amino acids, here we show that the very nature of a two-state cooperative transition such as a bimodal distribution from an exact free energy landscape and biphasic relaxation kinetics manifest in the thermodynamics and foldingunfolding kinetics of BBL and peripheral subunit-binding domain homologues. Our results provide an unequivocal resolution to the fundamental controversy related to the global downhill folding scheme, whose applicability to other proteins should be critically reexamined. 10.1073/pnas.0708480105

The X-ray crystal structure of RNA polymerase from Archaea

Akira Hirata — 2008-01-31T11:58:31-00:00

Nature (30 January 2008)

Chaos in a long-term experiment with a plankton community

Elisa Beninca — 2008-02-13T20:43:08-00:00

Nature, Vol. 451, No. 7180. (14 February 2008), pp. 822-825.

Structural identification of the pathway of long-range communication in an allosteric enzyme

Prafull Gandhi — 2008-02-13T10:34:48-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 6. (12 February 2008), pp. 1832-1837.

Allostery is a common mechanism of regulation of enzyme activity and specificity, and its signatures are readily identified from functional studies. For many allosteric systems, structural evidence exists of long-range communication among protein domains, but rarely has this communication been traced to a detailed pathway. The thrombin mutant D102N is stabilized in a self-inhibited conformation where access to the active site is occluded by a collapse of the entire 215219 -strand. Binding of a fragment of the protease activated receptor PAR1 to exosite I, 30-A away from the active site region, causes a large conformational change that corrects the position of the 215219 -strand and restores access to the active site. The crystal structure of the thrombin-PAR1 complex, solved at 2.2-A resolution, reveals the details of this long-range allosteric communication in terms of a network of polar interactions. 10.1073/pnas.0710894105

Intrinsically disordered gamma-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure

Jikui Song — 2008-02-13T10:31:38-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 5. (5 February 2008), pp. 1505-1510.

The retinal phosphodiesterase (PDE6) inhibitory gamma-subunit (PDEgamma) plays a central role in vertebrate phototransduction through alternate interactions with the catalytic alpha-subunits of PDE6 and the alpha-subunit of transducin (alphat). Detailed structural analysis of PDEgamma has been hampered by its intrinsic disorder. We present here the NMR solution structure of PDEgamma, which reveals a loose fold with transient structural features resembling those seen previously in the x-ray structure of PDEgamma4687 when bound to alphat in the transition-state complex. NMR mapping of the interaction between PDEgamma4687 and the chimeric PDE5/6 catalytic domain confirmed that C-terminal residues 7487 of PDEgamma are involved in the association and demonstrated that its W70 indole group, which is critical for subsequent binding to alphat, is left free at this stage. These results indicate that the interaction between PDEgamma and alphat during the phototransduction cascade involves the selection of preconfigured transient conformations. 10.1073/pnas.0709558105

Maps of random walks on complex networks reveal community structure

Martin Rosvall — 2008-01-24T08:30:08-00:00

Proceedings of the National Academy of Sciences (23 January 2008), 0706851105.

To comprehend the multipartite organization of large-scale biological and social systems, we introduce an information theoretic approach that reveals community structure in weighted and directed networks. We use the probability flow of random walks on a network as a proxy for information flows in the real system and decompose the network into modules by compressing a description of the probability flow. The result is a map that both simplifies and highlights the regularities in the structure and their relationships. We illustrate the method by making a map of scientific communication as captured in the citation patterns of >6,000 journals. We discover a multicentric organization with fields that vary dramatically in size and degree of integration into the network of science. Along the backbone of the networkincluding physics, chemistry, molecular biology, and medicineinformation flows bidirectionally, but the map reveals a directional pattern of citation from the applied fields to the basic sciences. 10.1073/pnas.0706851105

Cooperative binding of ATP and RNA induces a closed conformation in a DEAD box RNA helicase

Bettina Theissen — 2008-02-13T06:14:38-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 2. (15 January 2008), pp. 548-553.

RNA helicases couple the energy from ATP hydrolysis with structural changes of their RNA substrates. DEAD box helicases form the largest class of RNA helicases and share a helicase core comprising two RecA-like domains. An opening and closing of the interdomain cleft during RNA unwinding has been postulated but not shown experimentally. Single-molecule FRET experiments with the Bacillus subtilis DEAD box helicase YxiN carrying donor and acceptor fluorophores on different sides of the interdomain cleft reveal an open helicase conformation in the absence of nucleotides, or in the presence of ATP, or ADP, or RNA. In the presence of ADP and RNA, the open conformation is retained. By contrast, cooperative binding of ATP and RNA leads to a compact helicase structure, proving that the ATP- and ADP-bound states of RNA helicases display substantially different structures only when the RNA substrate is bound. These results establish a closure of the interdomain cleft in the helicase core at the beginning of the unwinding reaction, and suggest a conserved mechanism of energy conversion among DEAD box helicases across kingdoms. 10.1073/pnas.0705488105

Stepwise dynamics of epitaxially growing single amyloid fibrils

Miklos Kellermayer — 2008-02-13T05:35:39-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 1. (8 January 2008), pp. 141-144.

The assembly mechanisms of amyloid fibrils, tissue deposits in a variety of degenerative diseases, is poorly understood. With a simply modified application of the atomic force microscope, we monitored the growth, on mica surface, of individual fibrils of the amyloid 2535 peptide with near-subunit spatial and subsecond temporal resolution. Fibril assembly was polarized and discontinuous. Bursts of rapid (up to 300-nm1) growth phases that extended the fibril by approx7 nm or its integer multiples were interrupted with pauses. Stepwise dynamics were also observed for amyloid 142 fibrils growing on graphite, suggesting that the discontinuous assembly mechanisms may be a general feature of epitaxial amyloid growth. Amyloid assembly may thus involve fluctuation between a fast-growing and a blocked state in which the fibril is kinetically trapped because of intrinsic structural features. The used scanning-force kymography method may be adapted to analyze the assembly dynamics of a wide range of linear biopolymers. 10.1073/pnas.0704305105

The AAA+ superfamily -- a myriad of motions

Paul Tucker — 2007-12-04T23:05:25-00:00

Current Opinion in Structural Biology, Vol. 17, No. 6. (December 2007), pp. 641-652.

ATPases associated with various cellular activities are aptly named. They are the engines that drive processes such as protein degradation, protein refolding, [sigma]54-dependent transcriptional activation, DNA helicase activity, DNA replication initiation, and cellular cargo transport. Recent structural information derived from biochemical studies, electron microscopy (EM), small-angle X-ray scattering (SAXS), and X-ray crystallography are beginning to show how, at an atomic level, some of these systems use the conformational changes generated during the ATP hydrolysis cycle. Structural highlights in the processes mentioned are provided by work on ClpX and p97, ClpB, PspF and NtrC, RuvBL1, DnaA and the papillomavirus E1 initiator protein and dynein. The results emphasize the versatility of the AAA+ core domain.

Enhanced reaction kinetics in biological cells

C Loverdo — 2008-02-12T10:34:20-00:00

Nat Phys, Vol. 4, No. 2. (February 2008), pp. 134-137.

Alignment Uncertainty and Genomic Analysis

Karen Wong — 2008-01-25T07:09:02-00:00

Science, Vol. 319, No. 5862. (25 January 2008), pp. 473-476.

The statistical methods applied to the analysis of genomic data do not account for uncertainty in the sequence alignment. Indeed, the alignment is treated as an observation, and all of the subsequent inferences depend on the alignment being correct. This may not have been too problematic for many phylogenetic studies, in which the gene is carefully chosen for, among other things, ease of alignment. However, in a comparative genomics study, the same statistical methods are applied repeatedly on thousands of genes, many of which will be difficult to align. Using genomic data from seven yeast species, we show that uncertainty in the alignment can lead to several problems, including different alignment methods resulting in different conclusions. 10.1126/science.1151532

The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae

Jerome Mettetal — 2008-01-25T07:19:00-00:00

Science, Vol. 319, No. 5862. (25 January 2008), pp. 482-484.

The propagation of information through signaling cascades spans a wide range of time scales, including the rapid ligand-receptor interaction and the much slower response of downstream gene expression. To determine which dynamic range dominates a response, we used periodic stimuli to measure the frequency dependence of signal transduction in the osmo-adaptation pathway of Saccharomyces cerevisiae. We applied system identification methods to infer a concise predictive model. We found that the dynamics of the osmo-adaptation response are dominated by a fast-acting negative feedback through the kinase Hog1 that does not require protein synthesis. After large osmotic shocks, an additional, much slower, negative feedback through gene expression allows cells to respond faster to future stimuli. 10.1126/science.1151582

Programming biomolecular self-assembly pathways

Peng Yin — 2008-01-17T00:28:54-00:00

Nature, Vol. 451, No. 7176. (17 January 2008), pp. 318-322.

Structural Basis for Signal-Sequence Recognition by the Translocase Motor SecA as Determined by NMR

Ioannis Gelis — 2008-01-15T08:45:11-00:00

Cell, Vol. 131, No. 4. (16 November 2007), pp. 756-769.

Summary Recognition of signal sequences by cognate receptors controls the entry of virtually all proteins to export pathways. Despite its importance, this process remains poorly understood. Here, we present the solution structure of a signal peptide bound to SecA, the 204 kDa ATPase motor of the Sec translocase. Upon encounter, the signal peptide forms an [alpha]-helix that inserts into a flexible and elongated groove in SecA. The mode of binding is bimodal, with both hydrophobic and electrostatic interactions mediating recognition. The same groove is used by SecA to recognize a diverse set of signal sequences. Impairment of the signal-peptide binding to SecA results in significant translocation defects. The C-terminal tail of SecA occludes the groove and inhibits signal-peptide binding, but autoinhibition is relieved by the SecB chaperone. Finally, it is shown that SecA interconverts between two conformations in solution, suggesting a simple mechanism for polypeptide translocation.

Structure and dynamics of a molten globular enzyme.

Konstantin Pervushin — 2007-12-01T03:16:51-00:00

Nat Struct Mol Biol (11 November 2007)

Although protein dynamics has been recognized as a potentially important contributor to enzyme catalysis, structural disorder is generally considered to reduce catalytic efficiency. This widely held assumption has recently been challenged by the finding that an engineered chorismate mutase combines high catalytic activity with the properties of a molten globule, a loosely packed and highly dynamic conformational ensemble. Taking advantage of the ordering observed upon ligand binding, we have now used NMR spectroscopy to characterize this enzyme in complex with a transition-state analog. The complex adopts a helix-bundle structure, as designed, but retains unprecedented flexibility on the millisecond timescale across its entire length. Moreover, pre-steady-state kinetics data show that binding occurs by an induced-fit mechanism on the same timescale as the enzymatic reaction, linking global conformational plasticity with efficient catalysis.

Stability of the proteasome can be regulated allosterically through engagement of its proteolytic active sites

Maurits Kleijnen — 2007-12-06T17:53:38-00:00

Nature Structural & Molecular Biology, Vol. 14, No. 12. (18 November 2007), pp. 1180-1188.

Designed Protein-Protein Association

Dirk Grueninger — 2008-01-11T17:43:28-00:00

Science, Vol. 319, No. 5860. (11 January 2008), pp. 206-209.

The analysis of natural contact interfaces between protein subunits and between proteins has disclosed some general rules governing their association. We have applied these rules to produce a number of novel assemblies, demonstrating that a given protein can be engineered to form contacts at various points of its surface. Symmetry plays an important role because it defines the multiplicity of a designed contact and therefore the number of required mutations. Some of the proteins needed only a single side-chain alteration in order to associate to a higher-order complex. The mobility of the buried side chains has to be taken into account. Four assemblies have been structurally elucidated. Comparisons between the designed contacts and the results will provide useful guidelines for the development of future architectures. 10.1126/science.1150421

Real-time observation of bacteriophage T4 gp41 helicase reveals an unwinding mechanism

Timothee Lionnet — 2008-01-11T10:42:19-00:00

Proceedings of the National Academy of Sciences, Vol. 104, No. 50. (11 December 2007), pp. 19790-19795.

Helicases are enzymes that couple ATP hydrolysis to the unwinding of double-stranded (ds) nucleic acids. The bacteriophage T4 helicase (gp41) is a hexameric helicase that promotes DNA replication within a highly coordinated protein complex termed the replisome. Despite recent progress, the gp41 unwinding mechanism and regulatory interactions within the replisome remain unclear. Here we use a single tethered DNA hairpin as a real-time reporter of gp41-mediated dsDNA unwinding and single-stranded (ss) DNA translocation with 3-base pair (bp) resolution. Although gp41 translocates on ssDNA as fast as the in vivo replication fork (approx400 bp/s), its unwinding rate extrapolated to zero force is much slower (approx30 bp/s). Together, our results have two implications: first, gp41 unwinds DNA through a passive mechanism; second, this weak helicase cannot efficiently unwind the T4 genome alone. Our results suggest that important regulations occur within the replisome to achieve rapid and processive replication. 10.1073/pnas.0709793104

A mathematical tool for exploring the dynamics of biological networks

Paolo Barbano — 2007-11-22T12:53:12-00:00

Proceedings of the National Academy of Sciences (21 November 2007), 0709955104.

We have developed a mathematical approach to the study of dynamical biological networks, based on combining large-scale numerical simulation with nonlinear "dimensionality reduction" methods. Our work was motivated by an interest in the complex organization of the signaling cascade centered on the neuronal phosphoprotein DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of molecular weight 32,000). Our approach has allowed us to detect robust features of the system in the presence of noise. In particular, the global network topology serves to stabilize the net state of DARPP-32 phosphorylation in response to variation of the input levels of the neurotransmitters dopamine and glutamate, despite significant perturbation to the concentrations and levels of activity of a number of intermediate chemical species. Further, our results suggest that the entire topology of the network is needed to impart this stability to one portion of the network at the expense of the rest. This could have significant implications for systems biology, in that large, complex pathways may have properties that are not easily replicated with simple modules. 10.1073/pnas.0709955104

Construction of effective free energy landscape from single-molecule time series

Akinori Baba — 2007-12-05T10:59:10-00:00

Proceedings of the National Academy of Sciences, Vol. 104, No. 49. (4 December 2007), pp. 19297-19302.

A scheme for extracting an effective free energy landscape from single-molecule time series is presented. This procedure uniquely identifies a non-Gaussian distribution of the observable associated with each local equilibrium state (LES). Both the number of LESs and the shape of the non-Gaussian distributions depend on the time scale of observation. By assessing how often the system visits and resides in a chosen LES and escapes from one LES to another (with checking whether the local detailed balance is satisfied), our scheme naturally leads to an effective free energy landscape whose topography depends on in which time scale the system experiences the underlying landscape. For example, two metastable states are unified as one if the time scale of observation is longer than the escape time scale for which the system can visit mutually these two states. As an illustrative example, we present the application of extracting the effective free energy landscapes from time series of the end-to-end distance of a three-color, 46-bead model protein. It indicates that the time scales to attain the local equilibrium tend to be longer in the unfolded state than those in the compact collapsed state. 10.1073/pnas.0704167104

Visualizing spatially correlated dynamics that directs RNA conformational transitions

Qi Zhang — 2007-12-20T05:53:42-00:00

Nature, Vol. 450, No. 7173., pp. 1263-1267.

Allometric degree distributions facilitate food-web stability

Sonja Otto — 2007-12-20T05:53:44-00:00

Nature, Vol. 450, No. 7173., pp. 1226-1229.

Structural basis for gate-DNA recognition and bending by type IIA topoisomerases

Ken Dong — 2007-12-20T05:53:45-00:00

Nature, Vol. 450, No. 7173., pp. 1201-1205.

Coevolution with viruses drives the evolution of bacterial mutation rates

Csaba Pal — 2007-12-03T17:41:00-00:00

Nature (02 December 2007)

Crystal structure of the plasma membrane proton pump

Bjorn Pedersen — 2007-12-12T20:54:40-00:00

Nature, Vol. 450, No. 7172. (13 December 2007), pp. 1111-1114.

Crystal structure of the sodium–potassium pump

Preben Morth — 2007-12-14T05:49:39-00:00

Nature, Vol. 450, No. 7172., pp. 1043-1049.

Conformational dynamics of the KcsA potassium channel governs gating properties

Kent Baker — 2007-11-05T20:32:45-00:00

Nat Struct Mol Biol, Vol. 14, No. 11. (November 2007), pp. 1089-1095.

Molecular driving forces determining potassium channel slow inactivation

Julio Cordero-Morales — 2007-11-06T06:48:24-00:00

Nature Structural & Molecular Biology, Vol. 14, No. 11. (07 October 2007), pp. 1062-1069.

From the Cover: Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of alpha-helical and beta-sheet protein domains

Theodor Ackbarow — 2007-10-31T09:00:15-00:00

Proceedings of the National Academy of Sciences, Vol. 104, No. 42. (16 October 2007), pp. 16410-16415.

The fundamental fracture mechanisms of biological protein materials remain largely unknown, in part, because of a lack of understanding of how individual protein building blocks respond to mechanical load. For instance, it remains controversial whether the free energy landscape of the unfolding behavior of proteins consists of multiple, discrete transition states or the location of the transition state changes continuously with the pulling velocity. This lack in understanding has thus far prevented us from developing predictive strength models of protein materials. Here, we report direct atomistic simulation that over four orders of magnitude in time scales of the unfolding behavior of alpha-helical (AH) and [beta]-sheet (BS) domains, the key building blocks of hair, hoof, and wool as well as spider silk, amyloids, and titin. We find that two discrete transition states corresponding to two fracture mechanisms exist. Whereas the unfolding mechanism at fast pulling rates is sequential rupture of individual hydrogen bonds (HBs), unfolding at slow pulling rates proceeds by simultaneous rupture of several HBs. We derive the hierarchical Bell model, a theory that explicitly considers the hierarchical architecture of proteins, providing a rigorous structureproperty relationship. We exemplify our model in a study of AHs, and show that 34 parallel HBs per turn are favorable in light of the protein's mechanical and thermodynamical stability, in agreement with experimental findings that AHs feature 3.6 HBs per turn. Our results provide evidence that the molecular structure of AHs maximizes its robustness at minimal use of building materials. 10.1073/pnas.0705759104

A functional single-molecule binding assay via force spectroscopy

Yi Cao — 2007-11-20T11:18:27-00:00

Proceedings of the National Academy of Sciences, Vol. 104, No. 40. (2 October 2007), pp. 15677-15681.

Proteinligand interactions, including proteinprotein interactions, are ubiquitously essential in biological processes and also have important applications in biotechnology. A wide range of methodologies have been developed for quantitative analysis of proteinligand interactions. However, most of them do not report direct functional/structural consequence of ligand binding. Instead they only detect the change of physical properties, such as fluorescence and refractive index, because of the colocalization of protein and ligand, and are susceptible to false positives. Thus, important information about the functional state of proteinligand complexes cannot be obtained directly. Here we report a functional single-molecule binding assay that uses force spectroscopy to directly probe the functional consequence of ligand binding and report the functional state of proteinligand complexes. As a proof of principle, we used protein G and the Fc fragment of IgG as a model system in this study. Binding of Fc to protein G does not induce major structural changes in protein G but results in significant enhancement of its mechanical stability. Using mechanical stability of protein G as an intrinsic functional reporter, we directly distinguished and quantified Fc-bound and Fc-free forms of protein G on a single-molecule basis and accurately determined their dissociation constant. This single-molecule functional binding assay is label-free, nearly background-free, and can detect functional heterogeneity, if any, among proteinligand interactions. This methodology opens up avenues for studying proteinligand interactions in a functional context, and we anticipate that it will find broad application in diverse proteinligand systems. 10.1073/pnas.0705367104

Engineering Entropy-Driven Reactions and Networks Catalyzed by DNA

David Zhang — 2007-11-20T11:06:25-00:00

Science, Vol. 318, No. 5853. (16 November 2007), pp. 1121-1125.

Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics. 10.1126/science.1148532

Patterns of relative species abundance in rainforests and coral reefs

Igor Volkov — 2007-11-01T11:28:09-00:00

Nature, Vol. 450, No. 7166. (1 November 2007), pp. 45-49.

Kinetic redistribution of native and misfolded RNAs by a DEAD-box chaperone

Hari Bhaskaran — 2007-10-25T05:11:30-00:00

Nature, Vol. 449, No. 7165., pp. 1014-1018.

Quantifying the evolutionary dynamics of language

Erez Lieberman — 2007-10-10T22:28:15-00:00

Nature, Vol. 449, No. 7163. (11 October 2007), pp. 713-716.

Reconciling complexity with stability in naturally assembling food webs

Anje-Margriet Neutel — 2007-10-04T14:11:48-00:00

Nature, Vol. 449, No. 7162. (4 October 2007), pp. 599-602.