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Structures	Swiss-model
Domains	InterPro

HHV capsid portal protein
HHV capsid portal protein
Identifiers
Organism	?
Symbol	UL6
UniProt	P10190
Structures
Search for
Structures	Swiss-model
Domains	InterPro

HHV Capsid Portal Protein, or HSV-1 U_L-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 U_L-6 protein because it is the transcription product of Herpes gene U_L-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 U_L-6 is conserved across the family Herpesviridae and this family of genes is known as the "Herpesvirus UL6-like" gene family.^[9] "U_L-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 (U_L)".

Studies

pU_L-6 Amino acid range	Summary	Reference
Studies by amino acid sequence location
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		Nellissery, et al., 2007^[3]
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]
pU_L-26.5 "Scaffolding protein" Amino acid range	Summary	Reference
143-151	Deletion inhibits U_L-6 portal assembly	Singer, et al., 2005^[6]

Dodecameric structure

Research performed in 2004 used electron microscopy to predict that U_L-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 U_L-19 pentamer found at non-portal vertices.^[1]

Leucine zipper creates inter-protein adhesion

A study using deletion and mutation of the U_L-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 U_L-6 portals associate in vitro with viral protein U_L-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 U_L-6 with "scaffolding" protein U_L-26.5, amino acids 143 through 151.^[6]

Interaction with terminase complex

U_L-6 associates with a U_L-15/U_L-28 protein complex during capsid assembly. The U_L-15/U_L-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]