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Virus crystallisation

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units) of triangular “identical symmetrical units” to construct a 'spherical' shell to enclose some given material at any given size. In terms of optimising the ratio of number of required protein sub-assemblies and the surface area enclosed, icosahedral symmetry is again found to be the smallest and most efficient symmetry to adopt. Icosahedral capsid structure is an optimal design for encasing material due to its geometric and symmetric properties, lending to its efficient design being naturally and necessarily adopted by a majority of viral lineages. The symmetrical and highly-order nature of most virus crystals can be attributed to the inherent symmetry of the icosahedral capsid structure and its protein-protein interactions.
564: 74: 789: 224: 680: 426: 25: 881:, as they remain as prominent issues by placing limitations on crystal size variability. More emphasis is required on overcoming the limitations to macromolecular crystals, as its demand has been growing amongst researchers. Many viral crystals fall into this category, hence, the traditional crystallisation technique is said to receive more attention heading into the future. 780:, it is not enough to exceed that of X-ray crystallography. X-ray crystallography still remain as the most suitable approach when taking into account atomic level structures and micro-molecular interactions. Researchers therefore combine both cryo-EM and X-ray crystallisation as a method of overcoming each other's limitations. 475: 445:
genome. Due to the nature of packing identical asymmetric proteins with no rotational symmetry in order to minimise disturbance to protein-protein bonds at specific binding and receptor sites, capsid protein structures composed of a repetition of identical protein subunits necessarily arranges itself
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typically associated with life, such as cellular structure and independent metabolism. Overcoming limitations to virus crystallisation can provide important details about unknown molecular interactions that determine their life-like behaviour, thus allowing its characteristics to be comparable with
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capsid structure, specific geometric limitations naturally and necessarily apply on the possible conformations of the encasing structure. The icosahedral capsid structure is the most common arrangement due to 2-3-5 symmetry of its namesake shape, allowing for the use of up to the greatest number (60
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of scattered waves emitted in different directions across the lattice. Diffraction patterns depend on internal order within the crystal. High internal order with dense arrangements produce more extensive diffraction patterns with higher resolution, allowing for more precise determination of atomic
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Crystalline structures of virus crystals undergo imaging to produce visual results. They are developed to obtain information on microscopic arrangements in immobilized virus particles. Imaging has improved over time as advancements in X-ray sources, detectors and computer based imaging programs
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protruding from the extracellular aspect. Such viral envelope is usually acquired when travelling through the plasma or intracellular matrices of the host organism and may vary in composition depending on the host cell's membrane lipid content and host cell proteins. The structure of note for
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Duyvesteyn, Helen M. E.; Ginn, Helen M.; PietilÀ, Maija K.; Wagner, Armin; Hattne, Johan; Grimes, Jonathan M.; Hirvonen, Elina; Evans, Gwyndaf; Parsy, Marie-Laure; Sauter, Nicholas K.; Brewster, Aaron S.; Huiskonen, Juha T.; Stuart, David I.; Sutton, Geoff; Bamford, Dennis H. (2018-02-28).
813:. This is an alternative to cryo-EM that allows for visualisation of the environment and interaction outside of the virus inhabited host cell. Such advancements have propelled the understanding of virus activity in its host cell environment, rather than solely focusing on the virus itself. 796:
experiment: sample preparation, grid preparation, data collection, image processing, and structure determination. The reconstruction of a 3D density map is derived upon its 2D model, which allows for clearer visualisation of the structure for the sake of better understanding of its
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content on average. The solvent consists of water and other small molecules that freely diffuse through the crystal's interstitial spaces. Such unwanted presence of solvent-filled channels within macromolecular crystals hinder the reading of X-ray diffraction patterns.
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size have significant limitations compared to smaller crystals. They are softer and are more susceptible to damage, and can easily disintegrate over high radiation. This results from the significant amount of liquid between molecules, with approximately 50%
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to effectively analyze the structure and function behind viruses. Understanding of such characteristics have been enhanced thanks to the enhancement and diversity in crystallisation technologies. Virus crystals have a deep history of being widely applied in
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was difficult due to their relatively miniature size, with the smallest of viruses measuring in at roughly 20 nm in diameter. Microscopy was therefore a relatively challenging field, with alternative methods of observation in high demand.
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Viruses of specific species are placed in incubators with healthy cells, which mimics their ideal conditions for proper functioning. With the presence of healthy cells, viruses attach and undergo replication to produce large samples.
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The aim of crystallisation is to grow suitable sized, high quality virus crystals in order to be read properly during the imaging process. Artificial crystallisation in the laboratory is generally carried out in four major steps:
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The replicated virus particles are extracted, which is followed by purification to remove unwanted substances such as debris. This process isolates virus particles and leaves them in high concentration solutions. They then undergo
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sources, fast detectors, and innovative sample delivery methods to study the dynamic features of macromolecules. Such technique that observes virus dynamics rather than its static composition is referred to as
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structure through virus crystals that could diffract X-ray. This discovery served as a basis to continuous refinement in methods of virus crystallography, which later led to the determination of numerous other
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have also been involved in the image technology overhaul phase. MX is considered a new scientific discipline that adapts advanced tools and automated procedures. This is carried out with
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Whether or not viruses are ‘alive’ is a subject of heavy debate across the world. While viruses exhibit some behaviours that can be characterized as 'alive', such as their ability to
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In cryo-EM, crystallisation is not necessary and can directly observe biological samples, such as infected host cells and active viruses. This provides significant advantages over
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and other organic molecules) could diffract X-rays, implying a complex structural mechanism in viral bodies. This breakthrough served as the basis for the expansion of
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was developed during the mid 20th century by scientists' efforts to study the characteristics of crystallised viruses in laboratory investigations. Amongst them was
158:. These early observations were primarily regarded as laboratory curiosities. What began as mere curiosities evolved into the need for purification and isolation of 709:
of diffracted X-rays by individual atoms and virus particles. Precise atomic positions and arrangement of capsid proteins are generated under high resolution.
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Sehnke, Paul C.; Harrington, Melissa; Hosur, M.V.; Li, Yunge; Usha, R.; Craig Tucker, R.; Bomu, Wu; Stauffacher, Cynthia V.; Johnson, John E. (July 1988).
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in their 1962 crystallisation study was discovered to be composed of a '2 to 5 capsid protein subunit aggregate', arranged in a helical capsid structure.
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Erickson, John W.; Frankenberger, Elizabeth A.; Rossmann, Michael G.; Fout, G. Shay; Medappa, K. C.; Rueckert, Roland R. (February 1983).
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when investigating complex viral structures that pose challenges during crystallisation. It is particularly useful in observing the
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of viruses is facilitated by the crystallisation of viruses (and more specifically their capsid protein subunits) in order to study
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Concentrated virus pellets are treated with reagents that allow them to form small crystal nuclei. Such stages are referred to as
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of the capsid. Protein chains VP1, VP2, VP3, and VP4 individually derive from smaller structural protein components of the capsid.
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of a beam of electrons to detect and image a sample. Cryo-EM provides an overall improved performance over the traditional
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that folds to encase its contents in a helical structure, much like the naturally occurring helical structure seen in
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X-ray crystallography does not guarantee accurate performance for all virus crystals. For example, virus crystals at
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of the capsid proteins may also play a role in its organisation, though this has not yet been fully elucidated. The
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once initial crystal nuclei are formed. The growth of virus crystals can be influenced by various factors such as
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limitations of the packaging of the genome. Similar to the constraints that lend to the symmetrical nature of the
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Viruses generally invade and hijack host cells as a method of replication. Once infected, the host cell has its
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have expanded the extent in which virus morphology could be uncovered by researchers. Cryo-EM began to feature
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even in crystal form. It was during this time when researchers discovered that crystallised viruses (much like
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in the viral genome core, and are encased by a protective protein coat. Generally, the core is encased in
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and virology, and still to this day remains a catalyst for studying viral patterns to mitigate potential
654:. The growth process can take hours to days, depending on the virus and the crystallisation conditions. 563: 1680: 536: 1772:"Hydrophobic Interaction: A Promising Driving Force for the Biomedical Applications of Nucleic Acids" 1559:
Zandi, Roya; Reguera, David; Bruinsma, Robijn F.; Gelbart, William M.; Rudnick, Joseph (2004-11-02).
955:"Crystallization of a common cold virus, human rhinovirus 14: "Isomorphism" with poliovirus crystals" 714: 532: 1285: 730:
is used to measure the crystal's ability to diffract waves upon being exposed to the X-ray source.
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plates with prepared protein solutions for the Phase II Real-time Protein Crystal Growth experiment
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It was towards the end of the 20th century when scientists realized viruses surrounded with thick
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Zandi, Roya; van der Schoot, Paul; Reguera, David; Kegel, Willem; Reiss, Howard (March 2006).
870: 837: 770: 766: 684: 664: 618:, which needs to be overcome by hydrophobic interactions in order to crystallise the capsid. 329: 243: 212: 486:, a repeating subunit that makes up its spherical capsid structure. (Right) Image of the 3D 54: 2357: 2345: 2229: 2058: 1850: 1726: 1636: 1072: 1060: 966: 919: 727: 602:. This process is repeated until the precipitate is further densified into a virus pellet. 487: 455: 430: 251: 236: 228: 196: 188: 171: 78: 1137:"DĂ©couverte du premier virus, le virus de la mosaĂŻque du tabac : 1892 ou 1898 ?" 8: 833: 788: 718: 406: 333: 223: 82: 2361: 2233: 2193: 2160: 2062: 1854: 1730: 1640: 1076: 970: 923: 2386: 2318: 2258: 2131: 2098: 1879: 1838: 1804: 1771: 1747: 1714: 1657: 1624: 1463: 1444: 1411: 1261: 1228: 1213: 1194: 1101: 520: 495: 73: 2309: 1595: 1560: 1152: 997: 954: 2425: 2391: 2373: 2323: 2263: 2245: 2198: 2180: 2136: 2118: 2076: 2017: 2007: 1942: 1934: 1884: 1866: 1809: 1791: 1752: 1662: 1600: 1582: 1527: 1519: 1448: 1432: 1396: 1351: 1341: 1266: 1248: 1198: 1156: 1106: 1088: 1002: 984: 935: 931: 858: 849: 777: 722: 651: 544: 303: 276: 100:
particles. The crystals are composed of thousands of inactive forms of a particular
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Verdaguer, Nuria; Garriga, DamiĂ ; Fita, Ignacio (2013), Mateu, Mauricio G. (ed.),
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proteins in a single or double-layered structure. Some viruses, such as some
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with different geometries allow for different perspectives of visualisation. Both
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are produced from virus replication and propagation. This process consists of
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Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie
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Achieving clear visualisation of viruses using limited technology, such as
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enables scientists to visualise viruses at near-atomic resolution without
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The helical capsid structure is majorly dependent on the length of the
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Viruses are defined as “obligate intracellular parasites” that contain
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Virus crystals originate back to the late 19th century where the first
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However, despite Cryo-EM being able to provide higher resolution over
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in 2-fold symmetry view. Virus crystals amplify weak signals from the
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surrounding a layer of membrane-bound proteins, with either surface
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Guaita, Margherita; Watters, Scott C.; Loerch, Sarah (2022-12-01).
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X-ray crystallography utilizes virus crystals’ ability to diffract
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as a whole, and continue to be subject to heavy focus to this day.
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Rathore, Ishan; Mishra, Vandana; Bhaumik, Prasenjit (2021-05-10).
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of the virus, which is difficult to achieve via crystallisation.
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Xiao, Fan; Chen, Zhe; Wei, Zixiang; Tian, Leilei (August 2020).
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regions of molecules that associate with each other strongly in
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Louten, Jennifer (2016), "Virus Structure and Classification",
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in structure, with the second most common organisation being a
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when found in particular hosts. This membrane is composed of a
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Re-arrangement of viral components into solid crystal particles
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Ali, Asif; Chiang, Yi Wai; Santos, Rafael M. (February 2022).
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McPherson, Alexander; DeLucas, Lawrence James (2015-09-03).
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showing the asymmetrical capsid structural aggregate of the
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Schematic model showing the helical capsid structure of the
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Structure and Physics of Viruses: An Integrated Textbook
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Advancements in X-ray crystallography under the name of
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Goldsmith, Cynthia S.; Miller, Sara E. (October 2009).
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Stefano, George B.; Kream, Richard M. (October 2022).
1381:"Taxonomy, Classification and Nomenclature of Viruses" 250:, an expert in molecular microbiology, who determined 174:, which were the first ever viruses to be discovered. 77:
Comparison between crystallisation of salt (left) and
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International Committee on Taxonomy of Viruses (ICTV)
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Time resolved crystallography is facilitated through
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McPherson, Alexander; Gavira, Jose A. (2014-01-01).
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Biographical Memoirs of Fellows of the Royal Society
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McPherson, Alexander; Gavira, Jose A. (2014-01-01).
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Cold Spring Harbor Symposia on Quantitative Biology
877:, researchers are shifting their focus back to the 372:, also develop a large lipid membrane known as the 313:emerged as a new, alternative method for studying 302:Such viruses made it difficult to properly obtain 1332:Gelderblom, Hans R. 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Extraction and purification (isolation) 389:crystallisation and identification is the 2385: 2346:"Introduction to protein crystallization" 2317: 2257: 2192: 2130: 2070: 1878: 1803: 1746: 1656: 1594: 1576: 1498:Caspar, D. L. D.; Klug, A. 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(March 2016). 1387:, Elsevier, pp. 1730–1756, 1065:Acta Crystallographica Section F 807:direct electron detectors (DEDs) 23: 2402:from the original on 2024-03-27 2285: 2274:from the original on 2024-04-20 2209: 1983: 1953: 1763: 1673: 1538:from the original on 2024-03-27 1424: 1362:from the original on 2024-04-24 1167:from the original on 2024-04-10 1117:from the original on 2024-03-27 551:mechanisms of viral behaviour. 393:structure. 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(1999), 879:growing process of crystals 721:in this case refers to the 104:arranged in the shape of a 10: 2442: 1863:10.1038/s41598-018-21693-3 1625:"How Viruses Invade Cells" 854:certain essential features 687:determined structure of a 2370:10.1107/S2053230X13033141 2298:Current Neuropharmacology 2242:10.1107/S090904951004896X 2177:10.1016/j.sbi.2022.102484 1649:10.1016/j.bpj.2016.02.006 1431:Louten, Jennifer (2016), 1085:10.1107/S2053230X13033141 912:Journal of Crystal Growth 693:Enterobacteria phage PRD1 622:refer to the tendency of 555:Crystallisation procedure 92:is the re-arrangement of 1437:Essential Human Virology 1385:Encyclopedia of Virology 1245:10.1038/npjmgrav.2015.10 1187:Essential Human Virology 875:cryo-electron microscopy 620:Hydrophobic interactions 525:virally encoded proteins 421:Helical capsid structure 195:, who demonstrated that 177: 81:(right) as seen through 1578:10.1073/pnas.0405844101 857:those that belong to a 801:Recent advancements in 616:electrostatic repulsion 569:protein crystallography 164:protein crystallisation 136:protein crystallisation 38:, as no other articles 1967:. 2011. Archived from 1788:10.1002/advs.202001048 1393:10.1006/rwvi.1999.0277 1302:10.1098/rsbm.2002.0011 852:and evolve, they lack 798: 771:conformational changes 710: 572: 491: 434: 269:Human retrovirus (HIV) 240: 170:after the rise of the 86: 980:10.1073/pnas.80.4.931 871:X-ray crystallography 838:synchrotron radiation 791: 767:X-ray crystallography 715:electromagnetic waves 685:X-ray crystallography 682: 675:X-ray crystallography 665:X-ray crystallography 598:from the solid virus 566: 477: 428: 340:and behaviour in the 330:X-ray crystallography 309:In response to this, 244:X-ray crystallography 233:orthorhombic crystals 226: 213:X-ray crystallography 199:viruses retained its 125:Historical background 90:Virus crystallisation 76: 2115:10.1128/CMR.00027-09 1931:10.1042/etls20200316 1338:Medical Microbiology 728:X-ray diffractometer 488:icosahedral symmetry 456:Tobacco Mosaic Virus 431:Tobacco Mosaic virus 328:Combination of both 79:Tobacco Mosaic virus 2362:2014AcCrF..70....2M 2234:2011JSynR..18..101M 2072:10.3390/min12020205 2063:2022Mine...12..205A 1855:2018NatSR...8.3771D 1731:2006BpJ....90.1939Z 1719:Biophysical Journal 1641:2016BpJ...110.1028C 1629:Biophysical Journal 1571:(44): 15556–15560. 1439:, Elsevier: 19–29, 1189:, Elsevier: 19–29, 1077:2014AcCrF..70....2M 971:1983PNAS...80..931E 924:1988JCrGr..90..222S 83:electron microscopy 1843:Scientific Reports 1316:– via JSTOR. 859:biological kingdom 844:Undiscovered areas 799: 711: 683:Shown here is the 658:Imaging techniques 573: 537:tertiary structure 521:cellular processes 496:Icosahedral capsid 492: 435: 241: 87: 57:for suggestions. 47:to this page from 2304:(10): 1888–1893. 2013:978-94-007-6552-8 1454:978-0-12-800947-5 1402:978-0-12-227030-7 1347:978-0-9631172-1-2 1204:978-0-12-800947-5 778:light microscopes 634:4. Crystal growth 304:X-ray diffraction 119:disease outbreaks 71: 70: 2433: 2411: 2410: 2408: 2407: 2389: 2341: 2332: 2331: 2321: 2289: 2283: 2282: 2280: 2279: 2261: 2213: 2207: 2206: 2196: 2156: 2145: 2144: 2134: 2094: 2085: 2084: 2074: 2042: 2031: 2030: 2029: 2028: 1987: 1981: 1980: 1978: 1976: 1957: 1951: 1950: 1910: 1893: 1892: 1882: 1833: 1818: 1817: 1807: 1776:Advanced Science 1767: 1761: 1760: 1750: 1725:(6): 1939–1948. 1710: 1701: 1700: 1698: 1696: 1677: 1671: 1670: 1660: 1635:(5): 1028–1032. 1620: 1609: 1608: 1598: 1580: 1556: 1547: 1546: 1544: 1543: 1495: 1474: 1473: 1472: 1471: 1466: 1428: 1422: 1421: 1420: 1419: 1414: 1376: 1370: 1369: 1368: 1367: 1329: 1318: 1317: 1315: 1313: 1281: 1275: 1274: 1264: 1233:npj Microgravity 1224: 1218: 1217: 1216: 1182: 1176: 1175: 1173: 1172: 1132: 1126: 1125: 1123: 1122: 1104: 1056: 1011: 1010: 1000: 982: 950: 944: 943: 918:(1–3): 222–230. 903: 865:Future prospects 760:light microscope 592:centrifugalizing 338:virus morphology 315:virus structures 259:, including the 257:virus structures 227:Crystals of the 130:Pre-20th century 94:viral components 66: 63: 52: 50:related articles 27: 19: 2441: 2440: 2436: 2435: 2434: 2432: 2431: 2430: 2416: 2415: 2414: 2405: 2403: 2342: 2335: 2290: 2286: 2277: 2275: 2214: 2210: 2157: 2148: 2095: 2088: 2043: 2034: 2026: 2024: 2014: 1988: 1984: 1974: 1972: 1971:on 23 June 2022 1959: 1958: 1954: 1911: 1896: 1834: 1821: 1768: 1764: 1711: 1704: 1694: 1692: 1679: 1678: 1674: 1621: 1612: 1557: 1550: 1541: 1539: 1496: 1477: 1469: 1467: 1455: 1429: 1425: 1417: 1415: 1403: 1377: 1373: 1365: 1363: 1348: 1330: 1321: 1311: 1309: 1282: 1278: 1225: 1221: 1205: 1183: 1179: 1170: 1168: 1147:(10): 929–933. 1133: 1129: 1120: 1118: 1057: 1014: 951: 947: 904: 891: 887: 867: 846: 786: 749: 717:upon exposure. 702:Alphatectivirus 699:from the genus 677: 660: 557: 523:compromised as 517: 515:Viral behaviour 472: 423: 354: 323:crystallisation 297:lipid membranes 293: 281:antiviral drugs 273:viral infection 248:Dorothy Hodgkin 221: 193:Wendell Stanley 180: 132: 127: 67: 61: 58: 48: 45:introduce links 28: 17: 12: 11: 5: 2439: 2429: 2428: 2413: 2412: 2333: 2284: 2228:(2): 101–108. 2208: 2146: 2109:(4): 552–563. 2086: 2032: 2012: 1982: 1952: 1925:(1): 127–149. 1894: 1819: 1762: 1702: 1672: 1610: 1548: 1475: 1453: 1423: 1401: 1371: 1346: 1319: 1276: 1219: 1203: 1177: 1127: 1012: 965:(4): 931–934. 945: 888: 886: 883: 866: 863: 845: 842: 785: 782: 748: 745: 735:macromolecular 726:positions. An 676: 673: 659: 656: 576:1. Propagation 556: 553: 516: 513: 480:Ribbon diagram 471: 468: 422: 419: 391:capsid protein 386:spike proteins 353: 350: 292: 289: 237:cubic crystals 220: 217: 179: 176: 131: 128: 126: 123: 69: 68: 55:Find link tool 31: 29: 22: 15: 9: 6: 4: 3: 2: 2438: 2427: 2424: 2423: 2421: 2401: 2397: 2393: 2388: 2383: 2379: 2375: 2371: 2367: 2363: 2359: 2355: 2351: 2347: 2340: 2338: 2329: 2325: 2320: 2315: 2311: 2307: 2303: 2299: 2295: 2288: 2273: 2269: 2265: 2260: 2255: 2251: 2247: 2243: 2239: 2235: 2231: 2227: 2223: 2219: 2212: 2204: 2200: 2195: 2190: 2186: 2182: 2178: 2174: 2170: 2166: 2162: 2155: 2153: 2151: 2142: 2138: 2133: 2128: 2124: 2120: 2116: 2112: 2108: 2104: 2100: 2093: 2091: 2082: 2078: 2073: 2068: 2064: 2060: 2056: 2052: 2048: 2041: 2039: 2037: 2023: 2019: 2015: 2009: 2005: 2001: 1997: 1993: 1986: 1970: 1966: 1962: 1956: 1948: 1944: 1940: 1936: 1932: 1928: 1924: 1920: 1916: 1909: 1907: 1905: 1903: 1901: 1899: 1890: 1886: 1881: 1876: 1872: 1868: 1864: 1860: 1856: 1852: 1848: 1844: 1840: 1832: 1830: 1828: 1826: 1824: 1815: 1811: 1806: 1801: 1797: 1793: 1789: 1785: 1781: 1777: 1773: 1766: 1758: 1754: 1749: 1744: 1740: 1736: 1732: 1728: 1724: 1720: 1716: 1709: 1707: 1690: 1686: 1682: 1676: 1668: 1664: 1659: 1654: 1650: 1646: 1642: 1638: 1634: 1630: 1626: 1619: 1617: 1615: 1606: 1602: 1597: 1592: 1588: 1584: 1579: 1574: 1570: 1566: 1562: 1555: 1553: 1537: 1533: 1529: 1525: 1521: 1517: 1513: 1509: 1505: 1501: 1494: 1492: 1490: 1488: 1486: 1484: 1482: 1480: 1465: 1460: 1456: 1450: 1446: 1442: 1438: 1434: 1427: 1413: 1408: 1404: 1398: 1394: 1390: 1386: 1382: 1375: 1361: 1357: 1353: 1349: 1343: 1339: 1335: 1328: 1326: 1324: 1307: 1303: 1299: 1295: 1291: 1287: 1280: 1272: 1268: 1263: 1258: 1254: 1250: 1246: 1242: 1238: 1234: 1230: 1223: 1215: 1210: 1206: 1200: 1196: 1192: 1188: 1181: 1166: 1162: 1158: 1154: 1150: 1146: 1143:(in French). 1142: 1138: 1131: 1116: 1112: 1108: 1103: 1098: 1094: 1090: 1086: 1082: 1078: 1074: 1070: 1066: 1062: 1055: 1053: 1051: 1049: 1047: 1045: 1043: 1041: 1039: 1037: 1035: 1033: 1031: 1029: 1027: 1025: 1023: 1021: 1019: 1017: 1008: 1004: 999: 994: 990: 986: 981: 976: 972: 968: 964: 960: 956: 949: 941: 937: 933: 929: 925: 921: 917: 913: 909: 902: 900: 898: 896: 894: 889: 882: 880: 876: 872: 862: 860: 855: 851: 841: 839: 835: 830: 828: 823: 819: 814: 812: 808: 804: 795: 790: 781: 779: 774: 772: 768: 763: 761: 757: 754:utilizes the 753: 744: 741: 736: 731: 729: 724: 720: 716: 708: 704: 703: 698: 694: 690: 686: 681: 672: 670: 666: 655: 653: 649: 645: 641: 636: 635: 631: 629: 625: 621: 617: 613: 608: 607: 606:3. 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Index


orphan
link to it
introduce links
related articles
Find link tool

Tobacco Mosaic virus
electron microscopy
viral components
crystal
virus
prism
immunologists
epidemiology
disease outbreaks
protein crystallisation
Ritthausen
Osborne
hemoglobin
worms
fishes
proteins
protein crystallisation
virology
Tobacco Mosaic Viruses (TMV)
microscopy
TMV
Wendell Stanley
TMV

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