Capsid
A capsid or capsid (from Latin capsula , in German about 'small capsule') is a complex, regular structure made of proteins in viruses that is used to package the virus genome . A capsid is made up of a fixed number of protein subunits, the capsomeres . In the case of non-enveloped viruses, the capsid forms the outermost structure of the virus and is therefore responsible for attachment and penetration into the host cell ; With enveloped viruses, the capsid interacts with the outer virus envelope and often gives it the necessary stability.
The arrangement of the proteins in a capsid is based on different symmetries and is very diverse. These different structures and symmetries of capsids in turn have an impact on biological properties such as pathogenicity , the type of virus replication and environmental stability. The structure of the capsid also serves as a criterion for the classification of viruses within the virus taxonomy .
discovery
As early as the 1950s, Francis Crick and James Watson assumed that the packaging of the nucleic acid of viruses must consist of many identical subunits and that these must necessarily be arranged symmetrically. This arises from the consideration that the information on a nucleic acid can never suffice to code a single large protein which completely encloses this nucleic acid. The coding nucleic acid would mathematically always occupy a larger volume than the protein it encodes. The genetic information must therefore be used multiple times through many copies of identical proteins.
Capsomer
The capsomer (pl. Capsomer ) is the smallest regular unit from which a capsid is built and which determines its symmetry. In the simplest case, a capsid consists of identical capsomeres, which in turn only consist of one protein molecule. Very often, however, a capsomer consists of two to five different proteins that combine to form a regular capsid. The capsid can also be constructed from different capsomeres, e.g. B. Adenoviruses consist of two different capsomeres (pentons and hexones), which in turn consist of different virus proteins.
The individual subunits from which a capsomer can be built up are sometimes also referred to as protomers .
Given a given genome sequence of a virus, those proteins that form the capsomer can be recognized very easily, as they contain a high concentration of positively charged or basic amino acids ( arginine , lysine , histidine ) in certain sections . These basic protein domains of the capsid proteins (core proteins) are necessary for non- covalent binding to the negatively charged viral nucleic acid that is to be packaged.
Symmetry forms
Icosahedral symmetry
The most common symmetry of a capsid is a regular icosahedron (twenty surfaces), as this has the largest volume of all regular polyhedra for a given edge length. The edge length is determined by the size of the capsomeres and their number. When displaying virions in the electron microscope (EM) or by means of X-ray structure analysis, the appearance of many virus capsids, i.e. the external shape, does not correspond to an icosahedron, but is usually spherical, sometimes with protruding protein loops ( English spikes ). But if the same molecular positions of the capsomeres are connected to one another, an icosahedral arrangement of the capsomeres is found. It is therefore important to distinguish between the concept of the symmetry of a capsid and the shape ( morphology ) of a capsid . In the case of some viruses, the internal symmetry of an icosahedron can also be recognized immediately by its external shape, e.g. B. in members of the family Adenoviridae or some bacteriophages .
Most viral capsids with icosahedral symmetry are isometric ; H. all side edges of the icosahedron are of the same length. There are few examples that deviate from this (e.g. the T4 phage and its family Myoviridae ), whereby the icosahedron appears elongated and is therefore no longer an icosahedron in the geometric sense, but a pentagonal, bipyramidal antiprism . However, virologists speak of this form as a non-isometric icosahedron.
Axes of symmetry
 |
The structure of the icosahedron is characterized by three types of axes of symmetry , which show a rotational symmetry : through opposite side edges a symmetry axis with two-rayed (180 °) symmetry runs, through opposite side faces a three-rayed (120 °) and through opposite corners a five-rayed ( 72 °). The capsomeres or their arrangement on the icosahedron have the corresponding symmetries. For example, a capsid can be constructed from capsomeres with three-point or five-point symmetry; Often the capsomer forms within a capsid also have different symmetries depending on their position, since they usually consist of two, three or five identical protein subunits. The arrangement of the capsomeres to a certain rotational symmetry is not always necessarily determined by the structure of the proteins. With some virus capsids there are also different options for arranging them in an icosahedron, which is reflected in the formation of different virus particles with slightly different diameters in the same virus. The capsids of natural virions of the hepatitis B virus consist predominantly of 180 capsomeres (T = 3, see below), about 20% of the capsids, but of 240 capsomeres (T = 4). The biological significance of different capsid symmetries in the same virus has not yet been clarified.
Triangulation number
Felix as a capsid with the triangulation number T = 1
|
To describe an icosahedral capsid more precisely, a geometric number was introduced in 1962 by Donald Caspar and Aaron Klug , the so-called triangulation number (T). It can be used to describe the size and complexity of a capsid.
By assembling three identical molecules of any irregular, non-symmetrical protein, an equilateral (three-fold rotationally symmetrical ) triangle can be formed. This arrangement is the smallest possible symmetrical unit for the formation of an icosahedral capsid. Since such a regular triangle is made up of at least three subunits and an icosahedron consists of twenty such regular triangles, at least 3 · 20 = 60 such subunits are necessary to form the simplest icosahedral symmetry. This minimum number of 60 is described by the triangulation number T = 1. Larger and more complex capsids only have integer multiples of 60, e.g. B. often 180 (T = 3), 240 (T = 4), 960 (T = 16). The geometrically possible triangulation numbers result from the formula T = h² + hk + k², where h and k are whole numbers.
Helical symmetry
In some viruses, the capsomeres are arranged in a helical shape around the nucleic acid to be packaged in a helical quaternary structure ; in doing so, they form an elongated cylindrical shape on the outside . The diameter of a helical capsid is determined by the size of the capsomeres, the length of the cylinder is directly dependent on the length of the nucleic acid to be packaged.
Tobacco mosaic virus helical capsids
Scheme of a helical capsid
Several annular, helical capsids (blue) in arenaviruses
Non-enveloped (naked) helical capsids occur only in some plant viruses (e.g. tobacco mosaic virus , Lily Mottle virus ) and bacteriophages (family Inoviridae ), while viruses with an enveloped helical capsid are widespread in animals. Important pathogens with a helical capsid are, for example, the influenza viruses , the Paramyxoviridae (e.g. the mumps virus and measles virus ), the Bunyaviridae or Rhabdoviridae (e.g. the rabies virus ). The virus genus Torovirus has a special form of helical symmetry . Here a closed ring with the geometric shape of a torus is formed from an elongated helical capsid .
Complex or no symmetry
Some capsids have neither a clear icosahedral nor helical symmetry, despite the regular structure of their shape. This is particularly evident in members of the Poxviridae family (smallpox viruses). Hence the symmetry of these viruses is called "complex" .
The conical (conical) nucleocapsids in retroviruses , z. The HIV-1. The core protein of this virus can form tubes with helical symmetry in vitro , but it can also assume the natural shape of the conical, closed tube. This shows that this capsid is made up of a network of hexagons, which is interrupted by 12 net meshes with a pentagonal arrangement (marked in green in the figure). Of the twelve pentagonal gaps, seven are at the wide and five at the narrow end of the cone. This net symmetry thus follows a mathematical theorem of Leonhard Euler , according to which a closed surface that is to be covered by hexagons always has at least twelve pentagonal gaps ( Euler's polyhedron theorem ). The very variable angular relationships of the capsomeres to one another and the sites with lower stability created by the pentagons are likely to enable the release of the retrovirus genome into the cell nucleus.
In addition, there are viruses for which no clear capsid form could be detected. However, these viruses have proteins with the basic protein domains described above, which mediate between the nucleic acid and the virus envelope and are mostly anchored from the inside in the virus envelope. With this anchoring in the shell, they are related to the so-called matrix proteins which, in other viruses (e.g. Herpesviridae and Paramyxoviridae ), in addition to a capsid, line the shell from the inside; Strictly speaking, one should not speak of a capsid. For historical reasons, these proteins are usually referred to as core proteins . The best-known examples of this are the hepatitis C virus and the bovine viral diarrhea virus BVDV .
Capsid and nucleocapsid
The terms capsid and nucleocapsid are often incorrectly used synonymously. Only a capsid that is directly associated with the nucleic acid is also a nucleocapsid. There are viruses (e.g. the human immunodeficiency virus ) that have a second inside an outer capsid; here only this innermost is referred to as the nucleocapsid (or core ). Inside a capsid, the nucleic acid can also associate with basic proteins (e.g. cellular histones ) or be covalently linked to proteins. In this case one speaks of a nucleoprotein complex .
Energetic consideration of capsid formation
Capsids can form spontaneously and without energy consumption within a cell or experimentally as a purified protein solution of the capsomeres; This is often called self-assembly (Engl. self-assembly ), respectively. For the first time, the spontaneous capsid formation could be observed in the tobacco mosaic virus ; in vitro this was also later successful with animal viruses such as B. the alphaviruses .
In the case of a large number of viruses, however , this capsid formation did not succeed in vitro . It was found that for the capsomeres to assemble and to fold correctly, cellular proteins (so-called chaperones ) are necessary or only an association with nucleic acid leads to capsid formation.
Based on the fact that capsid formation can occur spontaneously and the symmetry of the icosahedron occurs particularly often, it was previously assumed that the capsid structure was the most energetically favorable state for the capsomeres. In fact, recent studies show that capsids correspond more to a metastable energetic state. This would also partly explain why capsids initially aggregate when the virus is discharged from the cell, whereas when the virus enters the cell, the same capsids spontaneously disintegrate again in order to release the viral nucleic acid. The energetically most unstable and limiting step for the self-assembly of an icosahedral capsid seems to be the incorporation of the last capsomeres for completion. This metastable state is also favored by the fact that a capsid only gains its stability from very weak interactions between the capsomeres.
After assembly, some capsids are phosphorylated on the outside or inside (e.g. in the case of the hepatitis B virus capsid ) by packaged ATP and phosphokinases , and in some cases also glycosylated by cellular enzymes ; these modifications also seem to influence the stability or desired instability of the capsids.
A special feature of some non-enveloped viruses or the in vitro synthesized capsids of enveloped viruses is the ability to crystallize . This observation led to discussions as early as the 1940s about the assignment of viruses to life forms, since otherwise only inanimate substances show the property of crystal formation. Crystallized capsids are essential in researching virus structure through X-ray structure analysis.
Biological significance of capsids
In addition to protecting the viral genome from DNA and RNA-cleaving enzymes ( nucleases ) and shaping enveloped viruses, capsids have some special biological functions and properties:
- In the case of non-enveloped viruses, the capsid forms the surface of a virion. As a result, it is directly exposed to attack by the immune system and acts as an antigen . In the case of viruses, the surface epitopes often change and thus escape the host's immune system, which is only possible to a very limited extent with naked capsids, since a number of changes in the capsid proteins can also lead to loss of stability or impairment of self-assembly . Non-enveloped viruses are therefore usually less variable in the surface epitopes than enveloped viruses.
- Since regularly arranged proteins represent a much stronger antigen than irregularly arranged proteins, capsids are particularly suitable as material for vaccinations .
- The capsid of non-enveloped viruses also mediates the binding to receptors of the target cell in order to initiate entry into the cell. With some enveloped DNA viruses, a special transport of the capsid to the nuclear pores ensures that the virus genome penetrates the cell nucleus.
- Due to the ability of capsids to act as transport vehicles for nucleic acids in cells , capsids generated in vitro , so-called virus-like particles (VLPs), are of particular interest in genetic engineering and gene therapy .
swell
literature
- DM Knipe, PM Howley (Eds.): Fields' Virology. 5th edition. 2 volumes, Philadelphia 2007, ISBN 978-0-7817-6060-7 .
- SJ Flint, LW Enquist, VR Racaniello, AM Skalka: Principles of Virology. Molecular Biology, Pathogenesis, and Control of Animal Viruses. 2nd Edition. ASM-Press, Washington DC 2004, ISBN 1-55581-259-7 .
- AJ Cann: Principles of Molecular Virology. 3. Edition. Academic Press, 2001, ISBN 0-12-158533-6 .
- A. Granoff, RG Webster (Ed.): Encyclopedia of Virology . (Volumes 1-3). San Diego 1999, ISBN 0-12-227030-4 .
- RH Cheng, T. Miyamura (Eds.): Structure-based study of viral replication . Singapore 2008, ISBN 978-981-270-405-4 .
- Roya Zandi, David Reguera et al .: Origin of icosahedral symmetry in viruses. PNAS (2004) 101 (44): pp. 15556-15560. PMID 15486087
Individual evidence
- ^ Francis Crick , James Watson : Structure of Small Viruses. Nature (1956) 177: pp. 473-475. PMID 13309339
- ↑ M. Newman, FM Suk, M. Cajimat, PK Chua, C. Shih: Stability and morphology comparisons of self-assembled virus-like particles from wild-type and mutant human hepatitis B virus capsid proteins. Journal of Virology. (2003) 77 (24): pp. 12950-12960. PMID 14645551
- ^ Donald LD Caspar, Aaron Klug: Physical Principles in the Construction of Regular Viruses . Cold Spring Harbor Symposia on Quantitative Biology XXVII, Cold Spring Harbor Laboratory, New York 1962, pp. 1-24.
- ^ BK Ganser, S. Li, VY Klishko et al .: Assembly and analysis of conical models for the HIV-1 core. Science (1999) 283 (5398): pp. 80-83. PMID 9872746
- ↑ E. Hiebert, JB Bancroft, CE Bracker: The assembly in vitro of some small spherical viruses, hybrid viruses, and other nucleoproteins. Virology (1968) 3: 492-508. PMID 5651027
- ↑ JR Lingappa, RL Martin, ML Wong, D. Ganem, WJ Welch, VR Lingappa: A eukaryotic cytosolic chaperonin is associated with a high molecular weight intermediate in the assembly of hepatitis B virus capsid, a multimeric particle. Journal of Cell Biology (1994) 125 (1): pp. 99-111. PMID 7908022 A Eukaryotic Cytosolic Chaperonin Is Associated with a High Molecular Weight Intermediate in the Assembly of Hepatitis B Virus Capsid, a Multimeric Particle.
- ↑ Robijn F. Bruinsma, William M. Gelbart: Viral self-assembly as a Thermodynamic Process . Physical Review Letters (2003) 90 (24): p. 248101 (e-pub) PMID 12857229
- ^ HD Nguyen, VS Reddy, CL III: Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids. Nano Lett. (2007) 7 (2): pp. 338-344. PMID 17297998
- ↑ P. Ceres, A. Zlotnick: Weak protein-protein interactions are sufficient to drive assembly of hepatitis B virus capsids. Biochemistry (2002) 41 (39): pp. 11525-11531. PMID 12269796
- ↑ Nadja Thönes, Anna Herreiner, Lysann Schädlich, Konrad Piuko, Martin Müller: A Direct Comparison of Human Papillomavirus Type 16 L1 Particles Reveals a Lower Immunogenicity of Capsomeres than Viruslike Particles with Respect to the Induced Antibody Response. J. Virol. (2008) 82 (11): pp. 5472–5485 PMC 2395182 (free full text)
Web links
- Gallery of various virus capsids as molecular models and X-ray structure analysis ( Memento from April 29, 2007 in the Internet Archive ) (from the ICTV report)
- Further tutorial on the triangulation number of capsids
- Examples for the calculation of capsid structures and triangulation numbers ( Memento from February 5, 2008 in the Internet Archive )
- SIB: Virus symmetry and T number , on: ViralZone
