Major capsid protein VP1

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Major capsid protein VP1
Mpyv colorbydepth.png
A rendering of an icosahedral viral capsid comprising 72 pentamers of murine polyomavirus VP1, colored such that areas of the surface closer to the interior center appear blue and areas further away appear red. Rendered from PDB: 1SIE ​.
Identifiers
SymbolVP1
Pfam PF00718
InterPro IPR000662
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome. [1] [2] [3]

Contents

Structure

VP1 is the major structural component of the polyomavirus icosahedral capsid, which has T=7 symmetry and a diameter of 40-45 nm. The capsid contains three proteins; VP1 is the primary component and forms a 360-unit outer capsid layer composed of 72 pentamers. The other two components, VP2 and VP3, have high sequence similarity to each other, with VP3 truncated at the N-terminus relative to VP2. VP2 and VP3 assemble inside the capsid in contact with VP1, [1] [2] with a stoichiometry of one VP2 or VP3 molecule to each pentamer. [4] [5] : 314  VP1 is capable of self-assembly into virus-like particles even in the absence of other viral components. [6] This process requires bound calcium ions and the resulting particles are stabilized by, but do not require, inter-pentamer disulfide bonds. [7]

The structure of an individual pentamer of the murine polyomavirus VP1 protein. Each monomer is colored differently. The conformationally flexible C-terminal arms are shown here in conformations compatible with binding to neighboring molecules. Superposed is a fragment of the polyomavirus VP2 protein (white), which binds to a pentamer oriented toward the central cavity. VP1 is from PDB: 1SIE ; VP2 is from PDB: 1CN3 1CN3 . Mpyv vp1 pentamer vp2 1sie 1cn3.png
The structure of an individual pentamer of the murine polyomavirus VP1 protein. Each monomer is colored differently. The conformationally flexible C-terminal arms are shown here in conformations compatible with binding to neighboring molecules. Superposed is a fragment of the polyomavirus VP2 protein (white), which binds to a pentamer oriented toward the central cavity. VP1 is from PDB: 1SIE ​; VP2 is from PDB: 1CN3 1CN3 ​.

The VP1 protein monomer is primarily composed of beta sheets folded into a jelly roll fold. Interactions between VP1 molecules within a pentamer involve extensive binding surfaces, mediated in part by interactions between edge beta-strands. The VP1 C-terminus is disordered and forms interactions between neighboring pentamers in the assembled capsid. The flexibility of the C-terminal arm will enable it to adopt different conformations in the six distinct interaction environments imposed by the symmetry of the icosahedral assembly. [4] [8] The C-terminus also contains a basic nuclear localization sequence, [5] : 316  while the N-terminus - which is oriented toward the center of the assembled capsid - contains basic residues that facilitate non-sequence-specific interactions with DNA. [9]

The same capsid structure as above, colored to illustrate the assembly of the icosahedral architecture from VP1 pentamers. Each symmetry-related VP1 monomer is shown in a different color. From PDB: 1SIE . Mpyv colorbychain.png
The same capsid structure as above, colored to illustrate the assembly of the icosahedral architecture from VP1 pentamers. Each symmetry-related VP1 monomer is shown in a different color. From PDB: 1SIE ​.

Function and trafficking

Murine polyomavirus VP1 in complex with the GT1a glycan. GT1a is shown in yellow and the VP1 monomer with a white surface and a blue protein backbone. A complex network of hydrogen bonds, many water-mediated, is shown at the binding surface by orange lines, with participating protein residues shown as sticks. Mutations of the two residues shown in cyan at the bottom of the figure can significantly affect pathogenicity. From PDB: 5CPW . Mpyv vp1 gt1a 5cpw.png
Murine polyomavirus VP1 in complex with the GT1a glycan. GT1a is shown in yellow and the VP1 monomer with a white surface and a blue protein backbone. A complex network of hydrogen bonds, many water-mediated, is shown at the binding surface by orange lines, with participating protein residues shown as sticks. Mutations of the two residues shown in cyan at the bottom of the figure can significantly affect pathogenicity. From PDB: 5CPW ​.

The VP1 protein is responsible for initiating the process of infecting a cell by binding to sialic acids in glycans, including some gangliosides, on the cell surface. [3] [8] [10] Canonically, VP1 interacts specifically with α(2,3)-linked and α(2,6)-linked sialic acids. [3] [8] In some cases additional factors are necessary conditions for viral entry; for example, JC virus requires the 5HT2A serotonin receptor for entry, although the specific mechanism of this requirement is unclear. [11] Once attached to the cell surface, the virions enter the cell and are trafficked by a retrograde pathway to the endoplasmic reticulum. The exact mechanism of endocytosis varies depending on the virus, and some viruses use multiple mechanisms; caveolae-dependent mechanisms are common. [12] The process by which polyomaviruses penetrate the membrane and exit the ER is not well understood, but conformational changes to VP1, possibly including reduction of its disulfide bonds, likely occur in the ER. For some polyomaviruses, VP1 has been detected reaching the nucleus along with the viral genome, though it is unclear how the genomic DNA disengages from VP1. [12]

All of the capsid proteins are expressed from the late region of the viral genome, so named because expression occurs only late in the infection process. VP1 has a nuclear localization sequence that enables import from the cytoplasm where it is synthesized by the host translation machinery to the cell nucleus where new virions are assembled. This nuclear import process, mediated by karyopherins, acts on assembled VP1 pentamers in complex with VP2 or VP3; oligomerization to form capsids occurs in the nucleus. [5] : 316–17 

Related Research Articles

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<span class="mw-page-title-main">Picornavirus</span> Family of viruses

Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.

<i>Polyomaviridae</i> Family of viruses

Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while others, such as Simian Virus 40, have been identified in humans to a lesser extent. Most of these viruses are very common and typically asymptomatic in most human populations studied. BK virus is associated with nephropathy in renal transplant and non-renal solid organ transplant patients, JC virus with progressive multifocal leukoencephalopathy, and Merkel cell virus with Merkel cell cancer.

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<i>Dependoparvovirus</i> Genus of viruses

Dependoparvovirus is a genus in the subfamily Parvovirinae of the virus family Parvoviridae; they are Group II viruses according to the Baltimore classification. Some dependoparvoviruses are also known as adeno-associated viruses because they cannot replicate productively in their host cell without the cell being coinfected by a helper virus such as an adenovirus, a herpesvirus, or a vaccinia virus.

Trichodysplasia spinulosa polyomavirus is a member virus of Human polyomavirus 8 that infects human hosts. First discovered in 2010, TSPyV is associated with Trichodysplasia spinulosa, a rare skin disease only seen in immunocompromised patients. The virus causes hyperproliferation and enlargement of hair follicles by modulating PP2A protein phosphatase signaling pathways. TSPyV was the eighth human polyomavirus to be discovered, and one of four associated with human disease, out of 13 human polyomaviruses known as of the 2015 update to polyomavirus taxonomy released by the International Committee on Taxonomy of Viruses.

<span class="mw-page-title-main">Murine polyomavirus</span> Species of virus

Murine polyomavirus is an unenveloped double-stranded DNA virus of the polyomavirus family. The first member of the family discovered, it was originally identified by accident in the 1950s. A component of mouse leukemia extract capable of causing tumors, particularly in the parotid gland, in newborn mice was reported by Ludwik Gross in 1953 and identified as a virus by Sarah Stewart and Bernice Eddy at the National Cancer Institute, after whom it was once called "SE polyoma". Stewart and Eddy would go on to study related polyomaviruses such as SV40 that infect primates, including humans. These discoveries were widely reported at the time and formed the early stages of understanding of oncoviruses.

<i>Avibirnavirus</i> Genus of viruses

Avibirnavirus is a genus of viruses in family Birnaviridae. There is a single species in this genus: Infectious bursal disease virus, which infects chickens and other fowl. It causes severe inflammation of the bursa of Fabricius, and causes considerable morbidity and mortality.

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KI polyomavirus is a virus of the family Polyomaviridae. It was discovered in 2007 in stored samples of human respiratory secretions collected by the Karolinska Institute, after which the virus is named.

MW polyomavirus is a virus of the polyomavirus family that infects human hosts. It was discovered in 2012 and reported independently by several research groups. It has been identified mostly in stool samples from children and has been detected in a variety of geographic locations.

STL polyomavirus is a virus of the polyomavirus family that infects human hosts. It was first reported in 2013 and is most closely related to MW polyomavirus. It has been identified mostly in stool samples from children and has been detected in a variety of geographic locations.

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A kinetic class, also known as a temporal class, is a grouping of genes in a viral genome that are expressed at the same time during the viral replication cycle. Five of the human DNA viral families have multiple kinetic classes: Poxviridae, Herpesviridae, Adenoviridae, Papillomaviridae, and Polyomaviridae. All of the genes in a particular kinetic class are activated by the same mechanism: either by the process of the virus entering the cell and uncoating, or by the products of an earlier kinetic class in what is known as a transcriptional cascade. Generally speaking, earlier kinetic classes code for enzymes that direct the viral replication process, and later kinetic classes code for structural proteins to be packaged into virions

<span class="mw-page-title-main">Large tumor antigen</span>

The large tumor antigen is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essential for viral proliferation. Containing four well-conserved protein domains as well as several intrinsically disordered regions, LTag is a fairly large multifunctional protein; in most polyomaviruses, it ranges from around 600-800 amino acids in length. LTag has two primary functions, both related to replication of the viral genome: it unwinds the virus's DNA to prepare it for replication, and it interacts with proteins in the host cell to dysregulate the cell cycle so that the host's DNA replication machinery can be used to replicate the virus's genome. Some polyomavirus LTag proteins - most notably the well-studied SV40 large tumor antigen from the SV40 virus - are oncoproteins that can induce neoplastic transformation in the host cell.

<span class="mw-page-title-main">Small tumor antigen</span>

The small tumor antigen is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. STag is expressed early in the infectious cycle and is usually not essential for viral proliferation, though in most polyomaviruses it does improve replication efficiency. The STag protein is expressed from a gene that overlaps the large tumor antigen (LTag) such that the two proteins share an N-terminal DnaJ-like domain but have distinct C-terminal regions. STag is known to interact with host cell proteins, most notably protein phosphatase 2A (PP2A), and may activate the expression of cellular proteins associated with the cell cycle transition to S phase. In some polyomaviruses - such as the well-studied SV40, which natively infects monkeys - STag is unable to induce neoplastic transformation in the host cell on its own, but its presence may increase the transforming efficiency of LTag. In other polyomaviruses, such as Merkel cell polyomavirus, which causes Merkel cell carcinoma in humans, STag appears to be important for replication and to be an oncoprotein in its own right.

The middle tumor antigen is a protein encoded in the genomes of some polyomaviruses, which are small double-stranded DNA viruses. MTag is expressed early in the infectious cycle along with two other related proteins, the small tumor antigen and large tumor antigen. MTag occurs only in a few known polyomaviruses, while STag and LTag are universal - it was first identified in mouse polyomavirus (MPyV), the first polyomavirus discovered, and also occurs in hamster polyomavirus. In MPyV, MTag is an efficient oncoprotein that can be sufficient to induce neoplastic transformation in some cells.

Minor capsid protein VP2 and minor capsid protein VP3 are viral proteins that are components of the polyomavirus capsid. Polyomavirus capsids are composed of three proteins; the major component is major capsid protein VP1, which self-assembles into pentamers that in turn self-assemble into enclosed icosahedral structures. The minor components are VP2 and VP3, which bind in the interior of the capsid.

Triatoma virus (TrV) is a virus belonging to the insect virus family Dicistroviridae. Within this family, there are currently 3 genera and 15 species of virus. Triatoma virus belongs to the genus Cripavirus. It is non-enveloped and its genetic material is positive-sense, single-stranded RNA. The natural hosts of triatoma virus are invertebrates. TrV is a known pathogen to Triatoma infestans, the major vector of Chagas disease in Argentina which makes triatoma virus a major candidate for biological vector control as opposed to chemical insecticides. Triatoma virus was first discovered in 1984 when a survey of pathogens of triatomes was conducted in the hopes of finding potential biological control methods for T. infestans.

References

  1. 1 2 Ramqvist T, Dalianis T (August 2009). "Murine polyomavirus tumour specific transplantation antigens and viral persistence in relation to the immune response, and tumour development". Seminars in Cancer Biology. 19 (4): 236–43. doi:10.1016/j.semcancer.2009.02.001. PMID   19505651.
  2. 1 2 Ramqvist T, Dalianis T (February 2010). "Lessons from immune responses and vaccines against murine polyomavirus infection and polyomavirus-induced tumours potentially useful for studies on human polyomaviruses". Anticancer Research. 30 (2): 279–84. PMID   20332429.
  3. 1 2 3 4 Buch MH, Liaci AM, O'Hara SD, Garcea RL, Neu U, Stehle T (October 2015). "Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity". PLOS Pathogens. 11 (10): e1005104. doi: 10.1371/journal.ppat.1005104 . PMC   4608799 . PMID   26474293.
  4. 1 2 Chen XS, Stehle T, Harrison SC (June 1998). "Interaction of polyomavirus internal protein VP2 with the major capsid protein VP1 and implications for participation of VP2 in viral entry". The EMBO Journal. 17 (12): 3233–40. doi:10.1093/emboj/17.12.3233. PMC   1170661 . PMID   9628860.
  5. 1 2 3 Almendral, José M. (2013). "Assembly of Simple Icosahedral Viruses". In Mateu, Mauricio G. (ed.). Structure and physics of viruses an integrated textbook. Dordrecht: Springer. ISBN   978-94-007-6552-8.
  6. ↑ Salunke DM, Caspar DL, Garcea RL (September 1986). "Self-assembly of purified polyomavirus capsid protein VP1". Cell. 46 (6): 895–904. doi:10.1016/0092-8674(86)90071-1. PMID   3019556. S2CID   25800023.
  7. ↑ Schmidt U, Rudolph R, Böhm G (February 2000). "Mechanism of assembly of recombinant murine polyomavirus-like particles". Journal of Virology. 74 (4): 1658–62. doi:10.1128/jvi.74.4.1658-1662.2000. PMC   111640 . PMID   10644335.
  8. 1 2 3 Stehle T, Harrison SC (February 1996). "Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments". Structure. 4 (2): 183–94. doi: 10.1016/s0969-2126(96)00021-4 . PMID   8805524.
  9. ↑ Moreland RB, Montross L, Garcea RL (March 1991). "Characterization of the DNA-binding properties of the polyomavirus capsid protein VP1". Journal of Virology. 65 (3): 1168–76. doi:10.1128/JVI.65.3.1168-1176.1991. PMC   239883 . PMID   1847446.
  10. ↑ Tsai B, Gilbert JM, Stehle T, Lencer W, Benjamin TL, Rapoport TA (September 2003). "Gangliosides are receptors for murine polyoma virus and SV40". The EMBO Journal. 22 (17): 4346–55. doi:10.1093/emboj/cdg439. PMC   202381 . PMID   12941687.
  11. ↑ Maginnis MS, Nelson CD, Atwood WJ (December 2015). "JC polyomavirus attachment, entry, and trafficking: unlocking the keys to a fatal infection". Journal of Neurovirology. 21 (6): 601–13. doi:10.1007/s13365-014-0272-4. PMC   4312552 . PMID   25078361.
  12. 1 2 Tsai B, Qian M (2010). "Cellular entry of polyomaviruses". Current Topics in Microbiology and Immunology. 343: 177–94. doi:10.1007/82_2010_38. ISBN   978-3-642-13331-2. PMID   20373089.
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