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Annual Review of Biophysics

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https://www.readbyqxmd.com/read/28532217/integration-of-bacterial-small-rnas-in-regulatory-networks
#1
Mor Nitzan, Rotem Rehani, Hanah Margalit
Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA-target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532216/structural-insights-into-the-eukaryotic-transcription-initiation-machinery
#2
Eva Nogales, Robert K Louder, Yuan He
Eukaryotic gene transcription requires the assembly at the promoter of a large preinitiation complex (PIC) that includes RNA polymerase II (Pol II) and the general transcription factors TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH. The size and complexity of Pol II, TFIID, and TFIIH have precluded their reconstitution from heterologous systems, and purification relies on scarce endogenous sources. Together with their conformational flexibility and the transient nature of their interactions, these limitations had precluded structural characterization of the PIC...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532215/matrix-mechanosensing-from-scaling-concepts-in-omics-data-to-mechanisms-in-the-nucleus-regeneration-and-cancer
#3
Dennis E Discher, Lucas Smith, Sangkyun Cho, Mark Colasurdo, Andrés J García, Sam Safran
Many of the most important molecules of life are polymers. In animals, the most abundant of the proteinaceous polymers are the collagens, which constitute the fibrous matrix outside cells and which can also self-assemble into gels. The physically measurable stiffness of gels, as well as tissues, increases with the amount of collagen, and cells seem to sense this stiffness. An understanding of this mechanosensing process in complex tissues, including fibrotic disease states with high collagen, is now utilizing 'omics data sets and is revealing polymer physics-type, nonlinear scaling relationships between concentrations of seemingly unrelated biopolymers...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532214/how-active-mechanics-and-regulatory-biochemistry-combine-to-form-patterns-in-development
#4
Peter Gross, K Vijay Kumar, Stephan W Grill
The development of organisms starting from their zygotic state involves a tight integration of the myriad biochemical signaling interactions with the mechanical forces that eventually pattern and shape the resulting embryo. In the past decade, it has become increasingly evident that several important developmental processes involve mechanical forces in an essential manner. In this review, we highlight the multifaceted role of mechanics in pattern formation, from protein and cell sorting to the generation of tissue shape...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532213/what-do-structures-tell-us-about-chemokine-receptor-function-and-antagonism
#5
Irina Kufareva, Martin Gustavsson, Yi Zheng, Bryan S Stephens, Tracy M Handel
Chemokines and their cell surface G protein-coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28532212/soft-matter-in-lipid-protein-interactions
#6
Michael F Brown
Membrane lipids and cellular water (soft matter) are becoming increasingly recognized as key determinants of protein structure and function. Their influences can be ascribed to modulation of the bilayer properties or to specific binding and allosteric regulation of protein activity. In this review, we first consider hydrophobic matching of the intramembranous proteolipid boundary to explain the conformational changes and oligomeric states of proteins within the bilayer. Alternatively, membranes can be viewed as complex fluids, whose properties are linked to key biological functions...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28399632/predicting-binding-free-energies-frontiers-and-benchmarks
#7
David L Mobley, Michael K Gilson
Binding free energy calculations based on molecular simulations provide predicted affinities for biomolecular complexes. These calculations begin with a detailed description of a system, including its chemical composition and the interactions among its components. Simulations of the system are then used to compute thermodynamic information, such as binding affinities. Because of their promise for guiding molecular design, these calculations have recently begun to see widespread applications in early-stage drug discovery...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375734/high-dimensional-mutant-and-modular-thermodynamic-cycles-molecular-switching-and-free-energy-transduction
#8
Charles W Carter
Understanding how distinct parts of proteins produce coordinated behavior has driven and continues to drive advances in protein science and enzymology. However, despite consensus about the conceptual basis for allostery, the idiosyncratic nature of allosteric mechanisms resists general approaches. Computational methods can identify conformational transition states from structural changes, revealing common switching mechanisms that impose multistate behavior. Thermodynamic cycles use factorial perturbations to measure coupling energies between side chains in molecular switches that mediate shear during domain motion...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28301770/imaging-and-optically-manipulating-neuronal-ensembles
#9
Luis Carrillo-Reid, Weijian Yang, Jae-Eun Kang Miller, Darcy S Peterka, Rafael Yuste
The neural code that relates the firing of neurons to the generation of behavior and mental states must be implemented by spatiotemporal patterns of activity across neuronal populations. These patterns engage selective groups of neurons, called neuronal ensembles, which are emergent building blocks of neural circuits. We review optical and computational methods, based on two-photon calcium imaging and two-photon optogenetics, to detect, characterize, and manipulate neuronal ensembles in three dimensions. We review data using these methods in the mammalian cortex that demonstrate the existence of neuronal ensembles in the spontaneous and evoked cortical activity in vitro and in vivo...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28301768/theory-and-modeling-of-rna-structure-and-interactions-with-metal-ions-and-small-molecules
#10
Li-Zhen Sun, Dong Zhang, Shi-Jie Chen
In addition to continuous rapid progress in RNA structure determination, probing, and biophysical studies, the past decade has seen remarkable advances in the development of a new generation of RNA folding theories and models. In this article, we review RNA structure prediction models and models for ion-RNA and ligand-RNA interactions. These new models are becoming increasingly important for a mechanistic understanding of RNA function and quantitative design of RNA nanotechnology. We focus on new methods for physics-based, knowledge-based, and experimental data-directed modeling for RNA structures and explore the new theories for the predictions of metal ion and ligand binding sites and metal ion-dependent RNA stabilities...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28301767/progress-in-human-and-tetrahymena-telomerase-structure-determination
#11
Henry Chan, Yaqiang Wang, Juli Feigon
Telomerase is an RNA-protein complex that extends the 3' ends of linear chromosomes, using a unique telomerase reverse transcriptase (TERT) and template in the telomerase RNA (TR), thereby helping to maintain genome integrity. TR assembles with TERT and species-specific proteins, and telomerase function in vivo requires interaction with telomere-associated proteins. Over the past two decades, structures of domains of TR and TERT as well as other telomerase- and telomere-interacting proteins have provided insights into telomerase function...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375732/rate-constants-and-mechanisms-of-protein-ligand-binding
#12
Xiaodong Pang, Huan-Xiang Zhou
Whereas protein-ligand binding affinities have long-established prominence, binding rate constants and binding mechanisms have gained increasing attention in recent years. Both new computational methods and new experimental techniques have been developed to characterize the latter properties. It is now realized that binding mechanisms, like binding rate constants, can and should be quantitatively determined. In this review, we summarize studies and synthesize ideas on several topics in the hope of providing a coherent picture of and physical insight into binding kinetics...
March 30, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375731/crispr-cas9-structures-and-mechanisms
#13
Fuguo Jiang, Jennifer A Doudna
Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems employ the dual RNA-guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific double-stranded breaks in target DNA. Target recognition strictly requires the presence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop formation and strand scission are driven by complementary base pairing between the guide RNA and target DNA, Cas9-DNA interactions, and associated conformational changes...
March 30, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375730/rna-structure-advances-and-assessment-of-3d-structure-prediction
#14
Zhichao Miao, Eric Westhof
Biological functions of RNA molecules are dependent upon sustained specific three-dimensional (3D) structures of RNA, with or without the help of proteins. Understanding of RNA structure is frequently based on 2D structures, which describe only the Watson-Crick (WC) base pairs. Here, we hierarchically review the structural elements of RNA and how they contribute to RNA 3D structure. We focus our analysis on the non-WC base pairs and on RNA modules. Several computer programs have now been designed to predict RNA modules...
March 30, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375729/long-range-interactions-in-riboswitch-control-of-gene-expression
#15
Christopher P Jones, Adrian R Ferré-D'Amaré
Riboswitches are widespread RNA motifs that regulate gene expression in response to fluctuating metabolite concentrations. Known primarily from bacteria, riboswitches couple specific ligand binding and changes in RNA structure to mRNA expression in cis. Crystal structures of the ligand binding domains of most of the phylogenetically widespread classes of riboswitches, each specific to a particular metabolite or ion, are now available. Thus, the bound states-one end point-have been thoroughly characterized, but the unbound states have been more elusive...
March 30, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375733/single-molecule-analysis-of-bacterial-dna-repair-and-mutagenesis
#16
Stephan Uphoff, David J Sherratt
Ubiquitous conserved processes that repair DNA damage are essential for the maintenance and propagation of genomes over generations. Then again, inaccuracies in DNA transactions and failures to remove mutagenic lesions cause heritable genome changes. Building on decades of research using genetics and biochemistry, unprecedented quantitative insight into DNA repair mechanisms has come from the new-found ability to measure single proteins in vitro and inside individual living cells. This has brought together biologists, chemists, engineers, physicists, and mathematicians to solve longstanding questions about the way in which repair enzymes search for DNA lesions and form protein complexes that act in DNA repair pathways...
March 24, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375735/single-molecule-studies-of-telomeres-and-telomerase
#17
Joseph W Parks, Michael D Stone
Telomeres are specialized chromatin structures that protect chromosome ends from dangerous processing events. In most tissues, telomeres shorten with each round of cell division, placing a finite limit on cell growth. In rapidly dividing cells, including the majority of human cancers, cells bypass this growth limit through telomerase-catalyzed maintenance of telomere length. The dynamic properties of telomeres and telomerase render them difficult to study using ensemble biochemical and structural techniques...
March 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375736/structures-of-large-protein-complexes-determined-by-nuclear-magnetic-resonance-spectroscopy
#18
Chengdong Huang, Charalampos G Kalodimos
Nuclear magnetic resonance (NMR) spectroscopy has been instrumental during the past two decades in providing high-resolution structures of protein complexes. It has been the method of choice for determining the structure of dynamic protein complexes, which are typically recalcitrant to other structural techniques. Until recently, NMR spectroscopy has yielded structures of small or medium-sized protein complexes, up to approximately 30-40 kDa. Major breakthroughs during the past decade, especially in isotopelabeling techniques, have enabled NMR characterization of large protein systems with molecular weights of hundreds of kDa...
March 17, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28301769/reconstructing-ancient-proteins-to-understand-the-causes-of-structure-and-function
#19
Georg K A Hochberg, Joseph W Thornton
A central goal in biochemistry is to explain the causes of protein sequence, structure, and function. Mainstream approaches rationalize sequence and structure by how they determine function and compare related proteins to find mechanisms underlying their functional differences. Although productive, both strategies suffer from intrinsic limitations that have left important aspects of many proteins unexplained. These limits can be overcome by reconstructing ancient proteins, experimentally characterizing their properties, and retracing their evolution through time...
March 15, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28301766/biophysical-models-of-protein-evolution-understanding-the-patterns-of-evolutionary-sequence-divergence
#20
Julian Echave, Claus O Wilke
For decades, rates of protein evolution have been interpreted in terms of the vague concept of functional importance. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic misfolding and misinteractions, linking their rate of evolution primarily to their abundance...
March 15, 2017: Annual Review of Biophysics
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