| 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 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 | |
| 322-416 | Deletion mutants form immature B-capsids which do contain portals | Nellissery, et al., 2007 | |
| 409-473 | |||
| L429, L436 | Mutation studies suggest putative leucine zipper required for portal ring formation | Nellissery, et al., 2007 | |
| 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 | |
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]
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]
Assembly of portal units is an initial step in constructing capsids of viral progeny. Capsids assembled in the absence of portals lack portals.[4]
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]
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]
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]