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Annual Review of Biophysics

Caleb J Bashor, James J Collins
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function...
March 16, 2018: Annual Review of Biophysics
Benjamin Stauch, Vadim Cherezov
G protein-coupled receptors (GPCRs) represent a large superfamily of membrane proteins that mediate cell signaling and regulate a variety of physiological processes in the human body. Structure-function studies of this superfamily were enabled a decade ago by multiple breakthroughs in technology that included receptor stabilization, crystallization in a membrane environment, and microcrystallography. The recent emergence of X-ray free-electron lasers (XFELs) has further accelerated structural studies of GPCRs and other challenging proteins by overcoming radiation damage and providing access to high-resolution structures and dynamics using micrometer-sized crystals...
March 15, 2018: Annual Review of Biophysics
Janna Kiselar, Mark R Chance
Hydroxyl radical footprinting (HRF) of proteins with mass spectrometry (MS) is a widespread approach for assessing protein structure. Hydroxyl radicals react with a wide variety of protein side chains, and the ease with which radicals can be generated (by radiolysis or photolysis) has made the approach popular with many laboratories. As some side chains are less reactive and thus cannot be probed, additional specific and nonspecific labeling reagents have been introduced to extend the approach. At the same time, advances in liquid chromatography and MS approaches permit an examination of the labeling of individual residues, transforming the approach to high resolution...
March 14, 2018: Annual Review of Biophysics
Tilman Kottke, Aihua Xie, Delmar S Larsen, Wouter D Hoff
The first stage in biological signaling is based on changes in the functional state of a receptor protein triggered by interaction of the receptor with its ligand(s). The light-triggered nature of photoreceptors allows studies on the mechanism of such changes in receptor proteins using a wide range of biophysical methods and with superb time resolution. Here, we critically evaluate current understanding of proton and electron transfer in photosensory proteins and their involvement both in primary photochemistry and subsequent processes that lead to the formation of the signaling state...
March 14, 2018: Annual Review of Biophysics
Po-Yi Ho, Jie Lin, Ariel Amir
Most microorganisms regulate their cell size. In this article, we review some of the mathematical formulations of the problem of cell size regulation. We focus on coarse-grained stochastic models and the statistics that they generate. We review the biologically relevant insights obtained from these models. We then describe cell cycle regulation and its molecular implementations, protein number regulation, and population growth, all in relation to size regulation. Finally, we discuss several future directions for developing understanding beyond phenomenological models of cell size regulation...
March 8, 2018: Annual Review of Biophysics
Jerome M Fox, Mengxia Zhao, Michael J Fink, Kyungtae Kang, George M Whitesides
Biomolecular recognition can be stubborn; changes in the structures of associating molecules, or the environments in which they associate, often yield compensating changes in enthalpies and entropies of binding and no net change in affinities. This phenomenon-termed enthalpy/entropy (H/S) compensation-hinders efforts in biomolecular design, and its incidence-often a surprise to experimentalists-makes interactions between biomolecules difficult to predict. Although characterizing H/S compensation requires experimental care, it is unquestionably a real phenomenon that has, from an engineering perspective, useful physical origins...
March 5, 2018: Annual Review of Biophysics
Venkata S Mandala, Jonathan K Williams, Mei Hong
Solid-state nuclear magnetic resonance (SSNMR) spectroscopy elucidates membrane protein structures and dynamics in atomic detail to yield mechanistic insights. By interrogating membrane proteins in phospholipid bilayers that closely resemble the biological membrane, SSNMR spectroscopists have revealed ion conduction mechanisms, substrate transport dynamics, and oligomeric interfaces of seven-transmembrane helix proteins. Research has also identified conformational plasticity underlying virus-cell membrane fusions by complex protein machineries, and β-sheet folding and assembly by amyloidogenic proteins bound to lipid membranes...
March 2, 2018: Annual Review of Biophysics
Sarah C Erlandson, Conor McMahon, Andrew C Kruse
G protein-coupled receptors (GPCRs), which mediate processes as diverse as olfaction and maintenance of metabolic homeostasis, have become the single most effective class of therapeutic drug targets. As a result, understanding the molecular basis for their activity is of paramount importance. Recent technological advances have made GPCR structural biology increasingly tractable, offering views of these receptors in unprecedented atomic detail. Structural and biophysical data have shown that GPCRs function as complex allosteric machines, communicating ligand-binding events through conformational change...
March 2, 2018: Annual Review of Biophysics
Yaser Hashem, Joachim Frank
Translation initiation in eukaryotes is a highly regulated and rate-limiting process. It results in the assembly and disassembly of numerous transient and intermediate complexes involving over a dozen eukaryotic initiation factors (eIFs). This process culminates in the accommodation of a start codon marking the beginning of an open reading frame at the appropriate ribosomal site. Although this process has been extensively studied by hundreds of groups for nearly half a century, it has been only recently, especially during the last decade, that we have gained deeper insight into the mechanics of the eukaryotic translation initiation process...
March 1, 2018: Annual Review of Biophysics
Mark A McLean, Michael C Gregory, Stephen G Sligar
The study of membrane proteins and receptors presents many challenges to researchers wishing to perform biophysical measurements to determine the structure, function, and mechanism of action of such components. In most cases, to be fully functional, proteins and receptors require the presence of a native phospholipid bilayer. In addition, many complex multiprotein assemblies involved in cellular communication require an integral membrane protein as well as a membrane surface for assembly and information transfer to soluble partners in a signaling cascade...
March 1, 2018: Annual Review of Biophysics
Max E Wilkinson, Pei-Chun Lin, Clemens Plaschka, Kiyoshi Nagai
The removal of noncoding introns from pre-messengerRNA(pre-mRNA) is an essential step in eukaryotic gene expression and is catalyzed by a dynamic multi-megadalton ribonucleoprotein complex called the spliceosome. The spliceosome assembles on pre-mRNA substrates by the stepwise addition of small nuclear ribonucleoprotein particles and numerous protein factors. Extensive remodeling is required to form the RNA-based active site and to mediate the pre-mRNA branching and ligation reactions. In the past two years, cryo-electron microscopy (cryo-EM) structures of spliceosomes captured in different assembly and catalytic states have greatly advanced our understanding of its mechanism...
March 1, 2018: Annual Review of Biophysics
Sander Boonstra, Jelle S Blijleven, Wouter H Roos, Patrick R Onck, Erik van der Giessen, Antoine M van Oijen
Influenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion...
March 1, 2018: Annual Review of Biophysics
Alex S Holehouse, Rohit V Pappu
Proteins can collapse into compact globules or form expanded, solvent-accessible, coil-like conformations. Additionally, they can fold into well-defined three-dimensional structures or remain partially or entirely disordered. Recent discoveries have shown that the tendency for proteins to collapse or remain expanded is not intrinsically coupled to their ability to fold. These observations suggest that proteins do not have to form compact globules in aqueous solutions. They can be intrinsically disordered, collapsed, or expanded, and even form well-folded, elongated structures...
January 18, 2018: Annual Review of Biophysics
Evelina Tutucci, Nathan M Livingston, Robert H Singer, Bin Wu
RNA is the fundamental information transfer system in the cell. The ability to follow single messenger RNAs (mRNAs) from transcription to degradation with fluorescent probes gives quantitative information about how the information is transferred fromDNAto proteins. This review focuses on the latest technological developments in the field of single-mRNA detection and their usage to study gene expression in both fixed and live cells. By describing the application of these imaging tools, we follow the journey of mRNA from transcription to decay in single cells, with single-molecule resolution...
January 18, 2018: Annual Review of Biophysics
Julien Béthune, Felix T Wieland
In eukaryotes, distinct transport vesicles functionally connect various intracellular compartments. These carriers mediate transport of membranes for the biogenesis and maintenance of organelles, secretion of cargo proteins and peptides, and uptake of cargo into the cell. Transport vesicles have distinct protein coats that assemble on a donor membrane where they can select cargo and curve the membrane to form a bud. A multitude of structural elements of coat proteins have been solved by X-ray crystallography...
January 18, 2018: Annual Review of Biophysics
A Joshua Wand, Kim A Sharp
Molecular recognition by proteins is fundamental to the molecular basis of biology. Dissection of the thermodynamic landscape governing protein-ligand interactions has proven difficult because determination of various entropic contributions is quite challenging. Nuclear magnetic resonance relaxation measurements, theory, and simulations suggest that conformational entropy can be accessed through a dynamical proxy. Here, we review the relationship between measures of fast side-chain motion and the underlying conformational entropy...
January 18, 2018: Annual Review of Biophysics
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
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
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
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
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