Biology:HHV capsid portal protein
| HHV capsid portal protein | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | ? | ||||||
| Symbol | UL6 | ||||||
| UniProt | P10190 | ||||||
| |||||||
HHV Capsid Portal Protein, or HSV-1 UL-6 protein, is the protein which forms a cylindrical portal in the capsid of Herpes simplex virus (HSV-1). The protein is commonly referred to as the HSV-1 UL-6 protein because it is the transcription product of Herpes gene UL-6.
The Herpes viral DNA enters and exits the capsid via the capsid portal. The capsid portal is formed by twelve copies of portal protein arranged as a ring; the proteins contain a leucine zipper sequence of amino acids which allow them to adhere to each other.[1] Each icosahedral capsid contains a single portal, located in one vertex.[2][3]
The portal is formed during initial capsid assembly and interacts with scaffolding proteins that construct the procapsid.[4] [5] [6] When the capsid is nearly complete, the viral DNA enters the capsid (i.e., the DNA is encapsidated) by a mechanism involving the portal and a DNA-binding protein complex similar to bacteriophage terminase.[7] Multiple studies suggest an evolutionary relationship between Capsid Portal Protein and bacteriophage portal proteins.[2][7]
When a virus infects a cell, it is necessary for the viral DNA to be released from the capsid. The Herpes virus DNA exits through the capsid portal.[8]
The genetic sequence of HSV-1 gene UL-6 is conserved across the family Herpesviridae and this family of genes is known as the "Herpesvirus UL6-like" gene family.[9] "UL-6" is nomenclature meaning that the protein is genetically encoded by the sixth (6th) open reading frame found in the viral genome segment named "Unique-Long (UL)".
Studies
| Studies by amino acid sequence location | ||
| pUL-6 Amino acid range | Summary | Reference |
|---|---|---|
| E121, A618, Q621 | Point mutations confer resistance to portal assembly inhibitor WAY-150138 | van Zeijl, et al., 2000[10] |
| 198-295 | Deletion mutant forms immature B-capsids with no portals | Nellissery, et al., 2007[3] |
| 322-416 | Deletion mutants form immature B-capsids which do contain portals | Nellissery, et al., 2007[3] |
| 409-473 | ||
| L429, L436 | Mutation studies suggest putative leucine zipper required for portal ring formation | Nellissery, et al., 2007[3] |
| R676 | Carboxyl (C)-terminal end | NCBI Sequence[11] |
| pUL-26.5 "Scaffolding protein" Amino acid range | Summary | Reference |
| 143-151 | Deletion inhibits UL-6 portal assembly | Singer, et al., 2005[6] |
Dodecameric structure
Research performed in 2004 used electron microscopy to predict that UL-6 forms 11, 12, 13, and 14-unit polymers. The dodecameric form was found to be most likely.[2]
Refinements to the electron microscopy in 2007 allowed finding that the portal is a twelve (12)-unit polymer present at one of the twelve capsid vertices instead of the UL-19 pentamer found at non-portal vertices.[1]
Leucine zipper creates inter-protein adhesion
A study using deletion and mutation of the UL-6 amino acid sequence demonstrated the leucine residues in a predicted leucine zipper motif were required for formation of the dodecameric ring structure.[3]
Early involvement in capsid assembly
Assembly of portal units is an initial step in constructing capsids of viral progeny. Capsids assembled in the absence of portals lack portals.[4]
Interaction with capsid scaffolding protein
In 2003, gel eletrophoresis studies demonstrated that intact UL-6 portals associate in vitro with viral protein UL-26. This association is antagonized by that action of WAY-150138, a thiourea inhibitor of HHV encapsidation.[5]
Further investigation during 2006 showed that assembly of capsid with portal depends on interaction of UL-6 with "scaffolding" protein UL-26.5, amino acids 143 through 151.[6]
Interaction with terminase complex
UL-6 associates with a UL-15/UL-28 protein complex during capsid assembly. The UL-15/UL-28 is believed to bind with viral DNA and serve the same purpose as terminase by packing viral DNA into the capsid during capsid assembly.[7]
Function during DNA egress
The DNA exits the capsid in a single linear segment. DNA exit may be controlled by UL-6 and dependent on temperature or environmental proteins.[8]
References
- ↑ 1.0 1.1 "Visualization of the herpes simplex virus portal in situ by cryo-electron tomography". Virology 361 (2): 426–34. 2007-05-10. doi:10.1016/j.virol.2006.10.047. PMID 17188319.
- ↑ 2.0 2.1 2.2 "Structure and polymorphism of the UL6 portal protein of herpes simplex virus type 1". Journal of Virology 78 (22): 12668–71. November 2004. doi:10.1128/JVI.78.22.12668-12671.2004. PMID 15507654.(Article: [1])
- ↑ 3.0 3.1 3.2 3.3 3.4 "A putative leucine zipper within the HSV-1 UL6 protein is required for portal ring formation". Journal of Virology 81 (17): 8868–77. 2007-06-20. doi:10.1128/JVI.00739-07. PMID 17581990.
- ↑ 4.0 4.1 "Involvement of the portal at an early step in herpes simplex virus capsid assembly". Journal of Virology 79 (16): 10540–6. August 2005. doi:10.1128/JVI.79.16.10540-10546.2005. PMID 16051846.
- ↑ 5.0 5.1 "Assembly of the herpes simplex virus capsid: identification of soluble scaffold-portal complexes and their role in formation of portal-containing capsids". Journal of Virology 77 (18): 9862–71. September 2003. doi:10.1128/JVI.77.18.9862-9871.2003. PMID 12941896. (Article: [2])
- ↑ 6.0 6.1 6.2 "Identification of a region in the herpes simplex virus scaffolding protein required for interaction with the portal". Journal of Virology 79 (1): 132–9. 2005. doi:10.1128/JVI.79.1.132-139.2005. PMID 15596809.
- ↑ 7.0 7.1 7.2 "Herpes Simplex Virus Type 1 Portal Protein UL6 Interacts with the Putative Terminase Subunits UL15 and UL28". Journal of Virology 77 (11): 6351–8. June 2003. doi:10.1128/JVI.77.11.6351-6358.2003. PMID 12743292.
- ↑ 8.0 8.1 "Uncoating the Herpes Simplex Virus Genome". Journal of Molecular Biology 370 (4): 633–42. 2007-05-13. doi:10.1016/j.jmb.2007.05.023. PMID 17540405.
- ↑ Herpesvirus UL6 like Conserved Domains view at NCBI
- ↑ Marja van Zeijl; Jeanette Fairhurst; Thomas R. Jones; Steven K. Vernon; John Morin; James LaRocque; Boris Feld; Bryan O'Hara et al. (October 2000). "Novel Class of Thiourea Compounds That Inhibit Herpes Simplex Virus Type 1 DNA Cleavage and Encapsidation: Resistance Maps to the UL6 Gene". Journal of Virology 74 (19): 9054–9061. doi:10.1128/JVI.74.19.9054-9061.2000. PMID 10982350.
- ↑ HSV-1 UL-6 amino acid sequence at NCBI
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