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- Volume 39, 2010
Annual Review of Biophysics - Volume 39, 2010
Volume 39, 2010
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Adventures in Physical Chemistry
Vol. 39 (2010), pp. 1–21More LessMy research has included chemical physics, electron and NMR spectroscopy, membrane biophysics, and immunology. This research was curiosity driven as well as problem and technique oriented. A theoretical equation was developed for relating nuclear hyperfine splittings to electron spin distributions in free radicals. Another equation was developed to relate NMR spectra to chemical reaction rates. Early evidence for the liquid-like properties of cell membranes was obtained through the use of paramagnetic probes (spin labels). Spin labels were used in measurements of lateral as well as transverse diffusion of phospholipids in bilayer membranes. Liquid-liquid phase separations were discovered in monolayer membranes containing phospholipids and cholesterol. In the area of immunology, it was shown that antigenic peptides bind to reconstituted class II MHC molecules in membranes and trigger specific T-helper cells.
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Global Dynamics of Proteins: Bridging Between Structure and Function
Vol. 39 (2010), pp. 23–42More LessBiomolecular systems possess unique, structure-encoded dynamic properties that underlie their biological functions. Recent studies indicate that these dynamic properties are determined to a large extent by the topology of native contacts. In recent years, elastic network models used in conjunction with normal mode analyses have proven to be useful for elucidating the collective dynamics intrinsically accessible under native state conditions, including in particular the global modes of motions that are robustly defined by the overall architecture. With increasing availability of structural data for well-studied proteins in different forms (liganded, complexed, or free), there is increasing evidence in support of the correspondence between functional changes in structures observed in experiments and the global motions predicted by these coarse-grained analyses. These observed correlations suggest that computational methods may be advantageously employed for assessing functional changes in structure and allosteric mechanisms intrinsically favored by the native fold.
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Simplified Models of Biological Networks
Vol. 39 (2010), pp. 43–59More LessThe function of living cells is controlled by complex regulatory networks that are built of a wide diversity of interacting molecular components. The sheer size and intricacy of molecular networks of even the simplest organisms are obstacles toward understanding network functionality. This review discusses the achievements and promise of a bottom-up approach that uses well-characterized subnetworks as model systems for understanding larger networks. It highlights the interplay between the structure, logic, and function of various types of small regulatory circuits. The bottom-up approach advocates understanding regulatory networks as a collection of entangled motifs. We therefore emphasize the potential of negative and positive feedback, as well as their combinations, to generate robust homeostasis, epigenetics, and oscillations.
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Compact Intermediates in RNA Folding
Vol. 39 (2010), pp. 61–77More LessLarge noncoding RNAs fold into their biologically functional structures via compact yet disordered intermediates, which couple the stable secondary structure of the RNA with the emerging tertiary fold. The specificity of the collapse transition, which coincides with the assembly of helical domains, depends on RNA sequence and counterions. It determines the specificity of the folding pathways and the magnitude of the free energy barriers to the ensuing search for the native conformation. By coupling helix assembly with nascent tertiary interactions, compact folding intermediates in RNA also play a crucial role in ligand binding and RNA-protein recognition.
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Nanopore Analysis of Nucleic Acids Bound to Exonucleases and Polymerases
Vol. 39 (2010), pp. 79–90More LessWhen a voltage is imposed across a thin membrane containing a nanoscopic pore, the electric field generated within the pore captures linear ionized polymers, such as nucleic acids, that are present in the solution bathing the pore. The nucleic acid molecule transiently blocks ionic current as it is translocated through the pore, and modulations of the current provide information about the structure and dynamic motion of the molecule. Altering the imposed voltage allows movement of the DNA molecule in the pore to be controlled. If a DNA-processing enzyme such as an exonuclease or polymerase is present, the enzyme-DNA complex is also drawn to the pore, and further modulations of the ionic current reflect enzyme function at the single-molecule level on millisecond timescales. The combined enzymatic and voltage control of a DNA molecule in the nanopore can be used to sequence the DNA.
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Actin Dynamics: From Nanoscale to Microscale
Vol. 39 (2010), pp. 91–110More LessThe dynamic nature of actin in cells manifests itself constantly. Polymerization near the cell edge is balanced by depolymerization in the interior, externally induced actin polymerization is followed by depolymerization, and spontaneous oscillations of actin at the cell periphery are frequently seen. I discuss how mathematical modeling relates quantitative measures of actin dynamics to the rates of underlying molecular level processes. The dynamic properties addressed include the rate of actin assembly at the leading edge of a moving cell, the disassembly rates of intracellular actin networks, the polymerization time course in externally stimulated cells, and spontaneous spatiotemporal patterns formed by actin. Although several aspects of actin assembly have been clarified by increasingly sophisticated models, our understanding of rapid actin disassembly is limited, and the origins of nonmonotonic features in externally stimulated actin polymerization remain unclear. Theory has generated several concrete, testable hypotheses for the origins of spontaneous actin waves and cell-edge oscillations. The development and use of more biomimetic systems applicable to the geometry of a cell will be key to obtaining a quantitative understanding of actin dynamics in cells.
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Eukaryotic Mechanosensitive Channels
Vol. 39 (2010), pp. 111–137More LessMechanosensitive ion channels are gated directly by physical stimuli and transduce these stimuli into electrical signals. Several criteria must apply for a channel to be considered mechanically gated. Mechanosensitive channels from bacterial systems have met these criteria, but few eukaryotic channels have been confirmed by the same standards. Recent work has suggested or confirmed that diverse types of channels, including TRP channels, K2P channels, MscS-like proteins, and DEG/ENaC channels, are mechanically gated. Several studies point to the importance of the plasma membrane for channel gating, but intracellular and/or extracellular structures may also be required.
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Protein Crystallization Using Microfluidic Technologies Based on Valves, Droplets, and SlipChip
Vol. 39 (2010), pp. 139–158More LessTo obtain protein crystals, researchers must search for conditions in multidimensional chemical space. Empirically, thousands of crystallization experiments are carried out to screen various precipitants at multiple concentrations. Microfluidics can manipulate fluids on a nanoliter scale, and it affects crystallization twofold. First, it miniaturizes the experiments that can currently be done on a larger scale and enables crystallization of proteins that are available only in small amounts. Second, it offers unique experimental approaches that are difficult or impossible to implement on a larger scale. Ongoing development of microfluidic techniques and their integration with protein production, characterization, and in situ diffraction promises to accelerate the progress of structural biology.
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Theoretical Perspectives on Protein Folding
Vol. 39 (2010), pp. 159–183More LessUnderstanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances in theory and experiments have resulted in a conceptual framework for describing the folding mechanisms of globular proteins. The sizes of proteins in the denatured and folded states, cooperativity of the folding transition, dispersions in the melting temperatures at the residue level, and timescales of folding are, to a large extent, determined by N, the number of residues. The intricate details of folding as a function of denaturant concentration can be predicted by using a novel coarse-grained molecular transfer model. By watching one molecule fold at a time, using single-molecule methods, investigators have established the validity of the theoretically anticipated heterogeneity in the folding routes and the N-dependent timescales for the three stages in the approach to the native state. Despite the successes of theory, of which only a few examples are documented here, we conclude that much remains to be done to solve the protein folding problem in the broadest sense.
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Bacterial Microcompartment Organelles: Protein Shell Structure and Evolution
Vol. 39 (2010), pp. 185–205More LessSome bacteria contain organelles or microcompartments consisting of a large virion-like protein shell encapsulating sequentially acting enzymes. These organized microcompartments serve to enhance or protect key metabolic pathways inside the cell. The variety of bacterial microcompartments provide diverse metabolic functions, ranging from CO2 fixation to the degradation of small organic molecules. Yet they share an evolutionarily related shell, which is defined by a conserved protein domain that is widely distributed across the bacterial kingdom. Structural studies on a number of these bacterial microcompartment shell proteins are illuminating the architecture of the shell and highlighting its critical role in controlling molecular transport into and out of microcompartments. Current structural, evolutionary, and mechanistic ideas are discussed, along with genomic studies for exploring the function and diversity of this family of bacterial organelles.
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Phase Separation in Biological Membranes: Integration of Theory and Experiment
Vol. 39 (2010), pp. 207–226More LessLipid bilayer model membranes that contain a single lipid species can undergo transitions between ordered and disordered phases, and membranes that contain a mixture of lipid species can undergo phase separations. Studies of these transformations are of interest for what they can tell us about the interaction energies of lipid molecules of different species and conformations. Nanoscopic phases (<200 nm) can provide a model for membrane rafts, specialized membrane domains enriched in cholesterol and sphingomyelin, which are believed to have essential biological functions in cell membranes. Crucial questions are whether lipid nanodomains can exist in stable equilibrium in membranes and what is the distribution of their sizes and lifetimes in membranes of different composition. Theoretical methods have supplied much information on these questions, but better experimental methods are needed to detect and characterize nanodomains under normal membrane conditions. This review summarizes linkages between theoretical and experimental studies of phase separation in lipid bilayer model membranes.
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Ribosome Structure and Dynamics During Translocation and Termination
Vol. 39 (2010), pp. 227–244More LessProtein biosynthesis, or translation, occurs on the ribosome, a large RNA-protein assembly universally conserved in all forms of life. Over the last decade, structures of the small and large ribosomal subunits and of the intact ribosome have begun to reveal the molecular details of how the ribosome works. Both cryo-electron microscopy and X-ray crystallography continue to provide fresh insights into the mechanism of translation. In this review, we describe the most recent structural models of the bacterial ribosome that shed light on the movement of messenger RNA and transfer RNA on the ribosome after each peptide bond is formed, a process termed translocation. We also discuss recent structures that reveal the molecular basis for stop codon recognition during translation termination. Finally, we review recent advances in understanding how bacteria handle errors in both translocation and termination.
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Expanding Roles for Diverse Physical Phenomena During the Origin of Life
Vol. 39 (2010), pp. 245–263More LessRecent synthetic approaches to understanding the origin of life have yielded insights into plausible pathways for the emergence of the first cells. Here we review current experiments with implications for the origin of life, emphasizing the ability of unexpected physical processes to facilitate the self-assembly and self-replication of the first biological systems. These laboratory efforts have uncovered novel physical mechanisms for the emergence of homochirality; the concentration and purification of prebiotic building blocks; and the ability of the first cells to assemble, grow, divide, and acquire greater complexity. In the absence of evolved biochemical capabilities, such physical processes likely played an essential role in early biology.
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Eukaryotic Chemotaxis: A Network of Signaling Pathways Controls Motility, Directional Sensing, and Polarity
Vol. 39 (2010), pp. 265–289More LessChemotaxis, the directed migration of cells in chemical gradients, is a vital process in normal physiology and in the pathogenesis of many diseases. Chemotactic cells display motility, directional sensing, and polarity. Motility refers to the random extension of pseudopodia, which may be driven by spontaneous actin waves that propagate through the cytoskeleton. Directional sensing is mediated by a system that detects temporal and spatial stimuli and biases motility toward the gradient. Polarity gives cells morphologically and functionally distinct leading and lagging edges by relocating proteins or their activities selectively to the poles. By exploiting the genetic advantages of Dictyostelium, investigators are working out the complex network of interactions between the proteins that have been implicated in the chemotactic processes of motility, directional sensing, and polarity.
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Protein Quantitation Using Isotope-Assisted Mass Spectrometry
Vol. 39 (2010), pp. 291–308More LessGenetic, chemical, and environmental perturbations can all induce large changes in cellular proteomes, and research aimed at quantifying these changes are an important part of modern biology. Although improvements in the hardware and software of mass spectrometers have produced increased throughput and accuracy of such measurements, new uses of heavy isotope internal standards that assist in this process have emerged. Surprisingly, even complex life forms such as mammals can be grown to near-complete replacement with heavy isotopes of common biological elements such as 15N, and these isotopically labeled organisms provide excellent controls for isolating and identifying experimental variables such as extraction or fractionation efficiencies. We discuss here the theory and practice of these technologies, as well as provide a review of significant recent biological applications.
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Structure and Activation of the Visual Pigment Rhodopsin
Vol. 39 (2010), pp. 309–328More LessRhodopsin is a specialized G protein–coupled receptor (GPCR) found in vertebrate rod cells. Absorption of light by its 11-cis retinal chromophore leads to rapid photochemical isomerization and receptor activation. Recent results from protein crystallography and NMR spectroscopy show how structural changes on the extracellular side of rhodopsin induced by retinal isomerization are coupled to the motion of membrane-spanning helices to create a G protein binding pocket on the intracellular side of the receptor. The signaling pathway provides a comprehensive explanation for the conservation of specific amino acids and structural motifs across the class A family of GPCRs, as well as for the conservation of selected residues within the visual receptor subfamily. The emerging model of activation indicates that, rather than being unique, the visual receptors provide a basis for understanding the common structural and dynamic elements in the class A GPCRs.
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Optical Control of Neuronal Activity
Vol. 39 (2010), pp. 329–348More LessAdvances in optics, genetics, and chemistry have enabled the investigation of brain function at all levels, from intracellular signals to single synapses, whole cells, circuits, and behavior. Until recent years, these research tools have been utilized in an observational capacity: imaging neural activity with fluorescent reporters, for example, or correlating aberrant neural activity with loss-of-function and gain-of-function pharmacological or genetic manipulations. However, optics, genetics, and chemistry have now combined to yield a new strategy: using light to drive and halt neuronal activity with molecular specificity and millisecond precision. Photostimulation of neurons is noninvasive, has unmatched spatial and temporal resolution, and can be targeted to specific classes of neurons. The optical methods developed to date encompass a broad array of strategies, including photorelease of caged neurotransmitters, engineered light-gated receptors and channels, and naturally light-sensitive ion channels and pumps. In this review, we describe photostimulation methods, their applications, and opportunities for further advancement.
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Biophysics of Knotting
Vol. 39 (2010), pp. 349–366More LessKnots appear in a wide variety of biophysical systems, ranging from biopolymers, such as DNA and proteins, to macroscopic objects, such as umbilical cords and catheters. Although significant advancements have been made in the mathematical theory of knots and some progress has been made in the statistical mechanics of knots in idealized chains, the mechanisms and dynamics of knotting in biophysical systems remain far from fully understood. We report on recent progress in the biophysics of knotting—the formation, characterization, and dynamics of knots in various biophysical contexts.
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Lessons Learned from UvrD Helicase: Mechanism for Directional Movement*
Vol. 39 (2010), pp. 367–385More LessHow do molecular motors convert chemical energy to mechanical work? Helicases and nucleic acids offer simple motor systems for extensive biochemical and biophysical analyses. Atomic resolution structures of UvrD-like helicases complexed with DNA in the presence of AMPPNP, ADP·Pi, and Pi reveal several salient points that aid our understanding of mechanochemical coupling. Each ATPase cycle causes two motor domains to rotationally close and open. At a minimum, two motor-track contact points of alternating tight and loose attachment convert domain rotations to unidirectional movement. A motor is poised for action only when fully in contact with its track and, if applicable, working against a load. The orientation of domain rotation relative to the track determines whether the movement is linear, spiral, or circular. Motors powered by ATPases likely deliver each power stroke in two parts, before and after ATP hydrolysis. Implications of these findings for analyzing hexameric helicase, F1F0 ATPase, and kinesin are discussed.
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Protein NMR Using Paramagnetic Ions
Vol. 39 (2010), pp. 387–405More LessParamagnetic metal ions offer outstanding opportunities for protein studies by nuclear magnetic resonance (NMR) spectroscopy. The paramagnetic effects manifested in the NMR spectra provide powerful restraints for the determination of the three-dimensional structure of proteins, open new possibilities for the analysis of protein-protein and protein-ligand interactions, and offer widely applicable tools for sensitivity enhancement of NMR experiments, resonance assignments, and studies of conformational heterogeneity and exchange. With the advent of new reagents for site-specific labeling of proteins with paramagnetic metal ions, a range of established and new strategies that used to be reserved for metalloproteins is becoming available for NMR spectroscopy of nonmetalloproteins.
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Previous Volumes
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Volume 52 (2023)
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Volume 51 (2022)
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Volume 50 (2021)
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Volume 49 (2020)
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Volume 48 (2019)
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Volume 47 (2018)
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Volume 46 (2017)
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Volume 45 (2016)
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Volume 44 (2015)
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Volume 43 (2014)
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Volume 42 (2013)
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Volume 41 (2012)
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Volume 40 (2011)
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Volume 39 (2010)
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Volume 38 (2009)
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Volume 37 (2008)
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Volume 36 (2007)
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Volume 35 (2006)
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Volume 34 (2005)
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Volume 33 (2004)
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Volume 32 (2003)
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Volume 31 (2002)
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Volume 30 (2001)
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Volume 29 (2000)
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Volume 28 (1999)
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Volume 27 (1998)
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Volume 26 (1997)
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Volume 25 (1996)
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Volume 24 (1995)
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Volume 23 (1994)
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Volume 22 (1993)
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Volume 21 (1992)
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Volume 20 (1991)
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Volume 19 (1990)
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Volume 18 (1989)
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Volume 17 (1988)
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Volume 16 (1987)
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Volume 15 (1986)
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Volume 14 (1985)
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Volume 13 (1984)
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Volume 12 (1983)
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Volume 11 (1982)
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Volume 10 (1981)
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Volume 9 (1980)
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Volume 8 (1979)
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Volume 7 (1978)
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Volume 6 (1977)
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Volume 5 (1976)
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Volume 4 (1975)
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Volume 3 (1974)
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Volume 2 (1973)
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Volume 1 (1972)
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Volume 0 (1932)