Herpesvirus Glycoprotein B
Encyclopedia
Herpesvirus glycoprotein B is a viral
glycoprotein
that is involved in the viral cell entry
of Herpes simplex virus
(HSV). Herpesviruses have an envelope
and an outer lipid bilayer
which contains twelve surface glycoproteins. For infectivity
to be attained, the double stranded DNA
genome of HSV must enter the host cell through means of fusion of its envelope with the cellular membrane or via endocytosis
. Other viral glycoproteins involved in the process of viral cell entry include gC,gB,gD,gH, and gL, but only gC,gB,gD, and gH are required for the fusion of the HSV's envelope with the cellular membrane. It can be noted that all herpesviruses have glycoproteins gB, gH, and gL.
with the signal sequence at the N terminus, based on DNA sequence analysis. Additionally, the protein contains an extra cytoplasmic N terminal domain, a transmembrane region, and a cytoplasmic C-terminal domain. Specifically, the HSV-1 glycoprotein B is a 904 amino acid
protein that has an extracellular domain which is composed of amino acids 31-730 and a cytoplasmic domain which contains amino acids 796-904. The HSV-2 glycoprotein B also has 904 amino acids with amino acids 23-727 comprising the extracellular domain and amino acids 793-904 spanning the cytoplasmic domain.
The crystal structure
of glycoprotein B's ectodomain
reveals an alpha-helical coiled-coil core and extended beta hairpins with hydrophobic tips. Due to its conformation, the glycoprotein B belongs to the class I viral membrane fusion glycoproteins as well as the class II fusion proteins.
. Glycoprotein B has two internal fusion loops, FL1 and FL2, which must undergo a conformational change for fusion to occur to the cellular membrane. The C-terminal of glycoprotein D becomes liberated when gD undergoes binding to one of three cellular receptors (nectin-1, HVEM, or a modified heparan sulfate). This C-terminal of gD may now interact with glycoprotein B and triggers molecular rearrangements which lead to fusion of the HSV envelope with the cellular membrane. The precise function of gB along with gH/gL are unknown but it is noted that they are both required for viral entry into the cell. The claim that gB is involved in fusion comes from the notable syncytial phenotype caused by certain mutations within the cytoplasmic domain of glycoprotein B.
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
that is involved in the viral cell entry
Viral entry
Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, the generalities are quite similar...
of Herpes simplex virus
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...
(HSV). Herpesviruses have an envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
and an outer lipid bilayer
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
which contains twelve surface glycoproteins. For infectivity
Infectivity
In epidemiology, infectivity refers to the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission that is, how frequently it spreads among hosts that are not in a parent-child relationship...
to be attained, the double stranded 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...
genome of HSV must enter the host cell through means of fusion of its envelope with the cellular membrane or via endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
. Other viral glycoproteins involved in the process of viral cell entry include gC,gB,gD,gH, and gL, but only gC,gB,gD, and gH are required for the fusion of the HSV's envelope with the cellular membrane. It can be noted that all herpesviruses have glycoproteins gB, gH, and gL.
Structure
The herpesvirus glycoprotein B is a 904 residue proteinProtein
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...
with the signal sequence at the N terminus, based on DNA sequence analysis. Additionally, the protein contains an extra cytoplasmic N terminal domain, a transmembrane region, and a cytoplasmic C-terminal domain. Specifically, the HSV-1 glycoprotein B is a 904 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
protein that has an extracellular domain which is composed of amino acids 31-730 and a cytoplasmic domain which contains amino acids 796-904. The HSV-2 glycoprotein B also has 904 amino acids with amino acids 23-727 comprising the extracellular domain and amino acids 793-904 spanning the cytoplasmic domain.
The crystal structure
Crystal structure
In mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...
of glycoprotein B's ectodomain
Ectodomain
An ectodomain is the domain of a membrane protein that extends into the extracellular space . Ectodomains are usually the part of a protein that initiate contact with surface which leads to signal transduction. In SARS-CoV the ectodomain of the spike protein is responsible for attachment to and...
reveals an alpha-helical coiled-coil core and extended beta hairpins with hydrophobic tips. Due to its conformation, the glycoprotein B belongs to the class I viral membrane fusion glycoproteins as well as the class II fusion proteins.
Function
The herpesvirus glycoprotein B is the most highly conserved of all surface glycoproteins on HSV and acts primarily as a fusion proteinFusion protein
Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...
. Glycoprotein B has two internal fusion loops, FL1 and FL2, which must undergo a conformational change for fusion to occur to the cellular membrane. The C-terminal of glycoprotein D becomes liberated when gD undergoes binding to one of three cellular receptors (nectin-1, HVEM, or a modified heparan sulfate). This C-terminal of gD may now interact with glycoprotein B and triggers molecular rearrangements which lead to fusion of the HSV envelope with the cellular membrane. The precise function of gB along with gH/gL are unknown but it is noted that they are both required for viral entry into the cell. The claim that gB is involved in fusion comes from the notable syncytial phenotype caused by certain mutations within the cytoplasmic domain of glycoprotein B.