E1 is one of two subunits of the envelope

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

found in the

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepatoc ...

. The other subunit is E2. This protein is a

type 1 transmembrane protein A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the org ...

with a highly glycosylated

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

ectodomain and a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

hydrophobic anchor. After being synthesized the E1 glycoproteins associates with the E2 glycoprotein as a noncovalent

heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...

Structure

The E1 glycoprotein residues 192-383 in the

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

1a H77 strain. After translation the E1 C-terminal

transmembrane domain A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...

s (TMDs) forms a

hairpin A hairpin or hair pin is a long device used to hold a person's hair in place. It may be used simply to secure long hair out of the way for convenience or as part of an elaborate hairstyle or coiffure. The earliest evidence for dressing the ha ...

of antiparallel a-helices. E1 is then cleaved by signal peptide

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...

at the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

and E1 is then made into a single long straight a-helix. What is known of the structure is from a

crystal structure In crystallography, crystal structure is a description of ordered arrangement of atoms, ions, or molecules in a crystalline material. Ordered structures occur from intrinsic nature of constituent particles to form symmetric patterns that repeat ...

made in 2014. This crystal structure shows that it has two a-helixes and 3 B-sheets for both

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

s; two

disulfide In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inorg ...

bridges stabilize these two monomers. This means that E1 is more compact then its E2 counterpart. It has been shown that E1 can fold with a small amount of E2 protein present. In addition to this it was shown that E1 oxidation preceded E2 maturation. This means that E1 has a chaperone-like role for E2. Despite these finds there are many things still unknown about the structure of E1. The E1 protein is anchored to the membrane. Most of the time E1 remains in its unfolded conformation.

Function

The E1 protein helps the virus attach to the membrane of the targeted cell. In other envelope virus the E1 protein has a similar role in helping the virus get into the cell. As a heterodimer with E2 it has been discovered that it is essential for HCV entry. When the heterodimer is formed the hepatitis C virus is then able to bind to the receptor of the cell. As a heterodimer the E1 protein alone with the E2 protein worked together to enter the cell. Also cleavage at the core-E1 junction is a prerequisite for SPP-catalyzed cleavage. This helps the virus relocate to the surface of lipid droplets. Once the virus gets to the surface of the lipid droplets it recruits the virus no-structural proteins and replication complex. The SP-catalyzed cleavage at the core-E1 junction is required for the formation of infectious particles and for the release of any HCV particles. Also E1 has no function with budding at the ER membrane. It also had no effect on the intracellular formation of

capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or m ...

-containing particles. Instead when E1 was not allowed to form this tended to facilitate the budding process.

Possible Vaccine

It has been shown that by blocking E1 we can prevent the formation of the envelope protein. There have been a number of studies trying to find the structure of E1. The hope for these vaccines is that they will be able to block the entry of Hepatitis C if they can block the formation of E1. If the virus cannot make the envelope protein then it will be unable to get into the host cells. The types of

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

s that would be used are synthetic peptide vaccines.

References

{{Viral proteins Viral structural proteins Hepatitis C virus