HHV capsid portal protein
{{Infobox nonhuman protein|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.
{{cite journal|title=Visualization of the herpes simplex virus portal in situ by cryo-electron tomography|vauthors=Cardone G, Winkler DC, Trus BL, Cheng N, Heuser JE, Newcomb WW, Brown JC, Steven AC |journal=Virology|date=2007-05-10|volume=361|issue=2|pmid=17188319|pages=426–34|doi=10.1016/j.virol.2006.10.047|pmc=1930166}}
Each icosahedral capsid contains a single portal, located in one vertex.{{cite journal|pmid=15507654|title=Structure and polymorphism of the UL6 portal protein of herpes simplex virus type 1|vauthors=Trus BL, Cheng N, Newcomb WW, Homa FL, Brown JC, Steven AC |journal=Journal of Virology|date=November 2004|volume=78|issue=22|pages=12668–71|doi=10.1128/JVI.78.22.12668-12671.2004|pmc=525097}}(Article: [http://jvi.asm.org/cgi/content/full/78/22/12668?view=long&pmid=15507654])
{{cite journal|journal=Journal of Virology|date=2007-06-20|title=A putative leucine zipper within the HSV-1 UL6 protein is required for portal ring formation|vauthors=Nellissery JK, Szczepaniak R, Lamberti C, Weller SK |pmid=17581990|volume=81|issue=17|pages=8868–77|doi=10.1128/JVI.00739-07|pmc=1951442}}
The portal is formed during initial capsid assembly and interacts with scaffolding proteins that construct the procapsid.
{{cite journal|title=Involvement of the portal at an early step in herpes simplex virus capsid assembly|vauthors=Newcomb WW, Homa FL, Brown JC |journal=Journal of Virology|volume=79|issue=16|date=August 2005|pmid=16051846|pages=10540–6|doi=10.1128/JVI.79.16.10540-10546.2005|pmc=1182615}}
{{cite journal|pmid=12941896|title=Assembly of the herpes simplex virus capsid: identification of soluble scaffold-portal complexes and their role in formation of portal-containing capsids|vauthors=Newcomb WW, Thomsen DR, Homa FL, Brown JC |journal=Journal of Virology|date=September 2003|volume=77|issue=18|pages=9862–71|doi=10.1128/JVI.77.18.9862-9871.2003|pmc=224603}} (Article: [http://jvi.asm.org/cgi/content/full/77/18/9862?view=long&pmid=12941896])
{{cite journal|pmid=15596809|title=Identification of a region in the herpes simplex virus scaffolding protein required for interaction with the portal|vauthors=Singer GP, Newcomb WW, Thomsen DR, Homa FL, Brown JC |journal=Journal of Virology|date=2005 |volume=79|issue=1|pages=132–9|doi=10.1128/JVI.79.1.132-139.2005|pmc=538710}}
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.
{{cite journal|pmid=12743292|title=Herpes Simplex Virus Type 1 Portal Protein UL6 Interacts with the Putative Terminase Subunits UL15 and UL28|vauthors=White CA, Stow ND, Patel AH, Hughes M, Preston VG |journal=Journal of Virology|date=June 2003|volume=77|issue=11|pages=6351–8|doi=10.1128/JVI.77.11.6351-6358.2003|pmc=154995}}
Multiple studies suggest an evolutionary relationship between Capsid Portal Protein and bacteriophage portal proteins.
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.
{{cite journal|title=Uncoating the Herpes Simplex Virus Genome|vauthors=Newcomb WW, Booy FP, Brown JC |journal=Journal of Molecular Biology|date=2007-05-13|pmid=17540405|volume=370|issue=4|pages=633–42|doi=10.1016/j.jmb.2007.05.023|pmc=1975772}}
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.[https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=65550 Herpesvirus UL6 like Conserved Domains view at NCBI] "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
| class = "wikitable" style = "float:left; font-size:85%; margin-left:15px width:65%"
| colspan="3"|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
{{cite journal|journal=Journal of Virology|title=Novel Class of Thiourea Compounds That Inhibit Herpes Simplex Virus Type 1 DNA Cleavage and Encapsidation: Resistance Maps to the UL6 Gene |author1=Marja van Zeijl |author2=Jeanette Fairhurst |author3=Thomas R. Jones |author4=Steven K. Vernon |author5=John Morin |author6=James LaRocque |author7=Boris Feld |author8=Bryan O'Hara |author9=Jonathan D. Bloom |author10=Stephen V. Johann |date=October 2000|volume=74|issue=19|pages=9054–9061|doi=10.1128/JVI.74.19.9054-9061.2000|pmid=10982350|pmc=102102}} | |
| 198-295 | Deletion mutant forms immature B-capsids with no portals | |
| 322-416 | rowspan="2"|Deletion mutants form immature B-capsids which do contain portals | |
| 409-473 | ||
| L429, L436 | Mutation studies suggest putative leucine zipper required for portal ring formation | |
| R676 | Carboxyl (C)-terminal end | NCBI Sequence[https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?view=gp&query_key=12&db=protein&dopt=GenPept&WebEnv=07lzcRIPJsPiwwdeXFv1ZrzdRvU7VudRpRMNAsmWcPOhu4WgAiQGk2rLf%40255D65F567DEBD90_0039SID&WebEnvRq=1&term=&tool=query&qty=1#sequence_136794 HSV-1 UL-6 amino acid sequence at NCBI] |
| pUL-26.5 "Scaffolding protein" Amino acid range | Summary | Reference |
| 143-151 | Deletion inhibits UL-6 portal assembly |
{{clear}}
=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.
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.
=Leucine zipper creates inter-protein adhesion=
=Early involvement in capsid assembly=
=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.
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.
= 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.
= Function during DNA egress =
References
{{Reflist|2}}
{{Viral proteins}}
{{DEFAULTSORT:Hhv Capsid Portal Protein}}