HHV capsid portal protein
Encyclopedia
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. Each icosahedral capsid contains a single portal, located in one vertex.
The portal is formed during initial capsid assembly and interacts with scaffolding proteins that construct the procapsid.
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. Multiple studies suggest an evolution
ary relationship between Capsid Portal Protein and bacteriophage portal proteins.
When 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.
The genetic sequence of HSV-1 gene UL-6 is conserved across the Herpesviridae family and this family of genes is known as the "Herpesvirus UL6-like" gene family. "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)".
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.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which forms a cylindrical portal in the capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
of Herpes simplex virus (HSV-1)
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
. The protein is commonly referred to as the HSV-1 UL-6 protein because it is the transcription product
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of Herpes gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
UL-6.
The Herpes viral DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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
Leucine zipper
A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...
sequence of amino acids which allow them to adhere to each other. Each icosahedral capsid contains a single portal, located in one vertex.
The portal is formed during initial capsid assembly and interacts with scaffolding proteins that construct the procapsid.
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
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
terminase. Multiple studies suggest an evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
ary relationship between Capsid Portal Protein and bacteriophage portal proteins.
When 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.
The genetic sequence of HSV-1 gene UL-6 is conserved across the Herpesviridae family and this family of genes is known as the "Herpesvirus UL6-like" gene family. "UL-6" is nomenclature
Nomenclature
Nomenclature is a term that applies to either a list of names or terms, or to the system of principles, procedures and terms related to naming - which is the assigning of a word or phrase to a particular object or property...
meaning that the protein is genetically
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
encoded by the sixth (6th) open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
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 |
| 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 Leucine zipper A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression... required for portal ring formation |
Nellissery, et al., 2007 |
| R676 | Carboxyl (C)-terminal end | NCBI Sequence |
| pUL-26.5 "Scaffolding protein" Amino acid range | Summary | Reference |
| 143-151 | Deletion inhibits UL-6 portal assembly | Singer, et al., 2005 |
Dodecameric structure
Research performed in 2004 used electron microscopy to predict that UL-6 forms 11, 12, 13, and 14-unit polymers. The dodecameric (twelve-unit) 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
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.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.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 thioureaThiourea
Thiourea is an organosulfur compound of with the formula SC2 . It is structurally similar to urea, except that the oxygen atom is replaced by a sulfur atom, but the properties of urea and thiourea differ significantly. Thiourea is a reagent in organic synthesis. "Thioureas" refers to a broad...
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.