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Annual Review of Biophysics

Alicia Alonso, Félix M Goñi
Ceramides are sphingolipids containing a sphingosine or a related base, to which a fatty acid is linked through an amide bond. When incorporated into a lipid bilayer, ceramides exhibit a number of properties not shared by almost any other membrane lipid: Ceramides (a) are extremely hydrophobic and thus cannot exist in suspension in aqueous media; (b) increase the molecular order (rigidity) of phospholipids in membranes; (c) give rise to lateral phase separation and domain formation in phospholipid bilayers; (d) possess a marked intrinsic negative curvature that facilitates formation of inverted hexagonal phases; (e) make bilayers and cell membranes permeable to small and large (i...
April 4, 2018: Annual Review of Biophysics
Adam James Waite, Nicholas W Frankel, Thierry Emonet
Living cells detect and process external signals using signaling pathways that are affected by random fluctuations. These variations cause the behavior of individual cells to fluctuate over time (behavioral variability) and generate phenotypic differences between genetically identical individuals (phenotypic diversity). These two noise sources reduce our ability to predict biological behavior because they diversify cellular responses to identical signals. Here, we review recent experimental and theoretical advances in understanding the mechanistic origin and functional consequences of such variation in Escherichia coli chemotaxis-a well-understood model of signal transduction and behavior...
April 4, 2018: Annual Review of Biophysics
Viktorija Globyte, Sung Hyun Kim, Chirlmin Joo
Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems...
March 29, 2018: Annual Review of Biophysics
Max Crispin, Andrew B Ward, Ian A Wilson
Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env) but also the numerous glycans that form a protective barrier on the Env protein. Because Env is heavily glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response...
March 29, 2018: Annual Review of Biophysics
David L Shis, Matthew R Bennett, Oleg A Igoshin
The ability of bacterial cells to adjust their gene expression program in response to environmental perturbation is often critical for their survival. Recent experimental advances allowing us to quantitatively record gene expression dynamics in single cells and in populations coupled with the mathematical modeling enable mechanistic understanding on how these responses are shaped by the underlying regulatory networks. Here, we review how the combination of local and global factors affect dynamical responses of gene regulatory networks...
March 23, 2018: Annual Review of Biophysics
Jeremy C Smith, Pan Tan, Loukas Petridis, Liang Hong
Dynamic neutron scattering directly probes motions in biological systems on femtosecond to microsecond timescales. When combined with molecular dynamics simulation and normal mode analysis, detailed descriptions of the forms and frequencies of motions can be derived. We examine vibrations in proteins, the temperature dependence of protein motions, and concepts describing the rich variety of motions detectable using neutrons in biological systems at physiological temperatures. New techniques for deriving information on collective motions using coherent scattering are also reviewed...
March 21, 2018: 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
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