Quarterly Reviews of Biophysics最新文献

{"title":"The theory of frame ordering: observing motions in calmodulin complexes.","authors":"Edward James d'Auvergne,&nbsp;Christian Griesinger","doi":"10.1017/S0033583519000015","DOIUrl":"https://doi.org/10.1017/S0033583519000015","url":null,"abstract":"<p><p>Large scale functional motions of molecules are studied experimentally using numerous molecular and biophysics techniques, the data from which are subsequently interpreted using diverse models of Brownian molecular dynamics. To unify all rotational physics techniques and motional models, the frame order tensor - a universal statistical mechanics theory based on the rotational ordering of rigid body frames - is herein formulated. The frame ordering is the fundamental physics that governs how motions modulate rotational molecular physics and it defines the properties and maximum information content encoded in the observable physics. Using the tensor to link residual dipolar couplings and pseudo-contact shifts, two distinct information-rich and atomic-level biophysical measurements from the field of nuclear magnetic resonance spectroscopy, to a number of basic mechanical joint models, a highly dynamic state of calmodulin (CaM) bound to a target peptide in a tightly closed conformation was observed. Intra- and inter-domain motions reveal the CaM complex to be entropically primed for peptide release.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"52 ","pages":"e3"},"PeriodicalIF":6.1,"publicationDate":"2019-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583519000015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39897403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygenic photosynthesis: history, status and perspective.","authors":"Wolfgang Junge","doi":"10.1017/S0033583518000112","DOIUrl":"https://doi.org/10.1017/S0033583518000112","url":null,"abstract":"<p><p>Cyanobacteria and plants carry out oxygenic photosynthesis. They use water to generate the atmospheric oxygen we breathe and carbon dioxide to produce the biomass serving as food, feed, fibre and fuel. This paper scans the emergence of structural and mechanistic understanding of oxygen evolution over the past 50 years. It reviews speculative concepts and the stepped insight provided by novel experimental and theoretical techniques. Driven by sunlight photosystem II oxidizes the catalyst of water oxidation, a hetero-metallic Mn4CaO5(H2O)4 cluster. Mn3Ca are arranged in cubanoid and one Mn dangles out. By accumulation of four oxidizing equivalents before initiating dioxygen formation it matches the four-electron chemistry from water to dioxygen to the one-electron chemistry of the photo-sensitizer. Potentially harmful intermediates are thereby occluded in space and time. Kinetic signatures of the catalytic cluster and its partners in the photo-reaction centre have been resolved, in the frequency domain ranging from acoustic waves via infra-red to X-ray radiation, and in the time domain from nano- to milli-seconds. X-ray structures to a resolution of 1.9 Å are available. Even time resolved X-ray structures have been obtained by clocking the reaction cycle by flashes of light and diffraction with femtosecond X-ray pulses. The terminal reaction cascade from two molecules of water to dioxygen involves the transfer of four electrons, two protons, one dioxygen and one water. A rigorous mechanistic analysis is challenging because of the kinetic enslaving at millisecond duration of six partial reactions (4e-, 1H+, 1O2). For the time being a peroxide-intermediate in the reaction cascade to dioxygen has been in focus, both experimentally and by quantum chemistry. Homo sapiens has relied on burning the products of oxygenic photosynthesis, recent and fossil. Mankind's total energy consumption amounts to almost one-fourth of the global photosynthetic productivity. If the average power consumption equalled one of those nations with the highest consumption per capita it was four times greater and matched the total productivity. It is obvious that biomass should be harvested for food, feed, fibre and platform chemicals rather than for fuel.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"52 ","pages":"e1"},"PeriodicalIF":6.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36887204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of CRISPR-Cas systems for genome editing and beyond","authors":"F. Zhang","doi":"10.1017/S0033583519000052","DOIUrl":"https://doi.org/10.1017/S0033583519000052","url":null,"abstract":"Abstract The development of clustered regularly interspaced short-palindromic repeat (CRISPR)-Cas systems for genome editing has transformed the way life science research is conducted and holds enormous potential for the treatment of disease as well as for many aspects of biotechnology. Here, I provide a personal perspective on the development of CRISPR-Cas9 for genome editing within the broader context of the field and discuss our work to discover novel Cas effectors and develop them into additional molecular tools. The initial demonstration of Cas9-mediated genome editing launched the development of many other technologies, enabled new lines of biological inquiry, and motivated a deeper examination of natural CRISPR-Cas systems, including the discovery of new types of CRISPR-Cas systems. These new discoveries in turn spurred further technological developments. I review these exciting discoveries and technologies as well as provide an overview of the broad array of applications of these technologies in basic research and in the improvement of human health. It is clear that we are only just beginning to unravel the potential within microbial diversity, and it is quite likely that we will continue to discover other exciting phenomena, some of which it may be possible to repurpose as molecular technologies. The transformation of mysterious natural phenomena to powerful tools, however, takes a collective effort to discover, characterize, and engineer them, and it has been a privilege to join the numerous researchers who have contributed to this transformation of CRISPR-Cas systems.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79199023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling the movement of molecules","authors":"R. Langer","doi":"10.1017/S0033583519000040","DOIUrl":"https://doi.org/10.1017/S0033583519000040","url":null,"abstract":"Abstract The ability to control the movement of molecules is both fascinating scientifically as well as being critically important to the well-being of our planet and its people. In particular, the sustained release of molecules over prolonged periods at controlled rates has had and will continue to have enormous implications for the delivery of substances in medicine, agriculture, the environment, nutrition, aquaculture, household consumer products, and numerous other areas. This field is advancing at a rapidly accelerating pace. In this article, I largely discuss our own work, starting 45 years ago, in enabling the controlled release of macromolecules from biocompatible polymers. I also discuss the synthesis of novel materials to affect molecular movement and I then examine external approaches for controlling the movement of molecules through materials, using forces such as electric, acoustic, and magnetic fields. I further discuss approaches for controlling molecular movement through physiologic barriers, such as the skin, lung, and intestine. Finally, I outline several future areas of this field, including how it can affect the developing world, the ability to control the movement of molecules into mammalian cells, and the design of intelligent approaches to control molecular delivery.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75940725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aggregation behavior of the amyloid model peptide NACore","authors":"Jon Pallbo, E. Sparr, U. Olsson","doi":"10.1017/S0033583519000039","DOIUrl":"https://doi.org/10.1017/S0033583519000039","url":null,"abstract":"Abstract The aggregation of the 11 residue long NACore peptide segment of α-synuclein (68-GAVVTGVTAVA-78) has been investigated using a combination of cryogenic transmission electron microscopy (cryo-TEM), small- and wide-angle X-ray scattering, and spectroscopy techniques. The aqueous peptide solubility is pH dependent, and aggregation was triggered by a pH quench from pH 11.3 to approximately pH 8 or 6, where the average peptide net charge is weakly negative (pH 8), or essentially zero (pH 6). Cryo-TEM shows the presence of long and stiff fibrillar aggregates at both pH, that are built up from β-sheets, as demonstrated by circular dichroism spectroscopy and thioflavin T fluorescence. The fibrils are crystalline, with a wide angle X-ray diffraction pattern that is consistent with a previously determined crystal structure of NACore. Of particular note is the cryo-TEM observation of small globular shaped aggregates, of the order of a few nanometers in size, adsorbed onto the surface of already formed fibrils at pH 6. The fibrillation kinetics is slow, and occurs on the time scale of days. Similarly slow kinetics is observed at both pH, but slightly slower at pH 6, even though the peptide solubility is here expected to be lower. The observation of the small globular shaped aggregates, together with the associated kinetics, could be highly relevant in relation to mechanisms of secondary nucleation and oligomer formation in amyloid systems.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"179 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80045586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annealing of ssDNA and compaction of dsDNA by the HIV-1 nucleocapsid and Gag proteins visualized using nanofluidic channels.","authors":"Kai Jiang,&nbsp;Nicolas Humbert,&nbsp;Sriram Kk,&nbsp;Thiebault Lequeu,&nbsp;Yii-Lih Lin,&nbsp;Yves Mely,&nbsp;Fredrik Westerlund","doi":"10.1017/S0033583518000124","DOIUrl":"https://doi.org/10.1017/S0033583518000124","url":null,"abstract":"<p><p>The nucleocapsid protein NC is a crucial component in the human immunodeficiency virus type 1 life cycle. It functions both in its processed mature form and as part of the polyprotein Gag that plays a key role in the formation of new viruses. NC can protect nucleic acids (NAs) from degradation by compacting them to a dense coil. Moreover, through its NA chaperone activity, NC can also promote the most stable conformation of NAs. Here, we explore the balance between these activities for NC and Gag by confining DNA-protein complexes in nanochannels. The chaperone activity is visualized as concatemerization and circularization of long DNA via annealing of short single-stranded DNA overhangs. The first ten amino acids of NC are important for the chaperone activity that is almost completely absent for Gag. Gag condenses DNA more efficiently than mature NC, suggesting that additional residues of Gag are involved. Importantly, this is the first single DNA molecule study of full-length Gag and we reveal important differences to the truncated Δ-p6 Gag that has been used before. In addition, the study also highlights how nanochannels can be used to study reactions on ends of long single DNA molecules, which is not trivial with competing single DNA molecule techniques.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"52 ","pages":"e2"},"PeriodicalIF":6.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37092602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roger Tsien – our colorful colleague 1952–2016","authors":"D. Lilley, B. Nordén","doi":"10.1017/S0033583517000154","DOIUrl":"https://doi.org/10.1017/S0033583517000154","url":null,"abstract":"Roger Tsien did more than anyone else in the application of fluorescent materials in biological sciences. He is undoubtedly best known for his development of the intrinsically fluorescent proteins and their many uses in cell biology and neurobiology. The original such protein is, of course, GFP, but Roger used genetic engineering methods to create a whole range of such proteins with different photophysical properties tuned to particular needs. In addition, he developed fluorescent probes such as Fura-2 that permitted calcium ions to be detected in cells, and this was extended to dyes that allowed the detection of other metal ions. Roger applied his science in medicine to great practical benefit, for example in the development of fluorescent peptides that would allow surgeons to visualize nerves thereby to avoid damaging them during surgery. His inventiveness extended to the commercial sector. Roger held many patents and was involved in setting up a number of companies. Roger Y. Tsien 1952–2016 Photo: The Royal Society.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"48 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2018-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78574914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The kink-turn in the structural biology of RNA.","authors":"Lin Huang,&nbsp;David M J Lilley","doi":"10.1017/S0033583518000033","DOIUrl":"https://doi.org/10.1017/S0033583518000033","url":null,"abstract":"<p><p>The kink-turn (k-turn) is a widespread structural motif found in functional RNA species. It typically comprises a three-nucleotide bulge followed by tandem trans sugar edge-Hoogsteen G:A base pairs. It introduces a sharp kink into the axis of duplex RNA, juxtaposing the minor grooves. Cross-strand H-bonds form at the interface, accepted by the conserved adenine nucleobases of the G:A basepairs. Alternative acceptors for one of these divides the k-turns into two conformational classes N3 and N1. The base pair that follows the G:A pairs (3b:3n) determines which conformation is adopted by a given k-turn. k-turns often mediate tertiary contacts in folded RNA species and frequently bind proteins. Common k-turn binding proteins include members of the L7Ae family, such as the human 15·5k protein. A recognition helix within these proteins binds in the widened major groove on the outside of the k-turn, that makes specific H-bonds with the conserved guanine nucleobases of the G:A pairs. L7Ae binds with extremely high affinity, and single-molecule data are consistent with folding by conformational selection. The standard, simple k-turn can be elaborated in a variety of ways, that include the complex k-turns and the k-junctions. In free solution in the absence of added metal ions or protein k-turns do not adopt the tightly-kinked conformation. They undergo folding by the binding of proteins, by the formation of tertiary contacts, and some (but not all) will fold on the addition of metal ions. Whether or not folding occurs in the presence of metal ions depends on local sequence, including the 3b:3n position, and the -1b:-1n position (5' to the bulge). In most cases -1b:-1n = C:G, so that the 3b:3n position is critical since it determines both folding properties and conformation. In general, the selection of these sequence matches a given k-turn to its biological requirements. The k-turn structure is now very well understood, to the point at which they can be used as a building block for the formation of RNA nano-objects, including triangles and squares.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e5"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37092597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folding of copper proteins: role of the metal?","authors":"Candan Ariöz,&nbsp;Pernilla Wittung-Stafshede","doi":"10.1017/S0033583518000021","DOIUrl":"https://doi.org/10.1017/S0033583518000021","url":null,"abstract":"<p><p>Copper is a redox-active transition metal ion required for the function of many essential human proteins. For biosynthesis of proteins coordinating copper, the metal may bind before, during or after folding of the polypeptide. If the metal binds to unfolded or partially folded structures of the protein, such coordination may modulate the folding reaction. The molecular understanding of how copper is incorporated into proteins requires descriptions of chemical, thermodynamic, kinetic and structural parameters involved in the formation of protein-metal complexes. Because free copper ions are toxic, living systems have elaborate copper-transport systems that include particular proteins that facilitate efficient and specific delivery of copper ions to target proteins. Therefore, these pathways become an integral part of copper protein folding in vivo. This review summarizes biophysical-molecular in vitro work assessing the role of copper in folding and stability of copper-binding proteins as well as protein-protein copper exchange reactions between human copper transport proteins. We also describe some recent findings about the participation of copper ions and copper proteins in protein misfolding and aggregation reactions in vitro.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e4"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37092601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper chaperone blocks amyloid formation via ternary complex.","authors":"Istvan Horvath,&nbsp;Tony Werner,&nbsp;Ranjeet Kumar,&nbsp;Pernilla Wittung-Stafshede","doi":"10.1017/S0033583518000045","DOIUrl":"https://doi.org/10.1017/S0033583518000045","url":null,"abstract":"<p><p>Protein misfolding in cells is avoided by a network of protein chaperones that detect misfolded or partially folded species. When proteins escape these control systems, misfolding may result in protein aggregation and amyloid formation. We here show that aggregation of the amyloidogenic protein α-synuclein (αS), the key player in Parkinson's disease, is controlled by the copper transport protein Atox1 in vitro. Copper ions are not freely available in the cellular environment, but when provided by Atox1, the resulting copper-dependent ternary complex blocks αS aggregation. Because the same inhibition was found for a truncated version of αS, lacking the C-terminal part, it appears that Atox1 interacts with the N-terminal copper site in αS. Metal-dependent chaperoning may be yet another manner in which cells control its proteome.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e6"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37092600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}