Hepatitis B virus DNA polymerase is a

hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...

viral protein A viral protein is both a component and a product of a virus. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. ...

. It is a

DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to crea ...

that can use either DNA or RNA templates and a

ribonuclease H Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/ DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearl ...

that cuts RNA in the duplex. Both functions are supplied by the

reverse transcriptase A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genom ...

(RT) domain.

Structure

The hepadnaviral P protein is organized into three domains: an N-terminal domain () covering the terminal and the spacer, an RT domain related to every other

domain, and a C-terminal domain () regulating the RNase H activity. Furthermore, hepadnavirus polymerases contain a terminal protein (TP) domain that contains a

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

residue that serves as a primer for the synthesis of the (-) DNA strand.

Function

The Hepatitis B virus (HBV) polymerase is a multifunctional

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

, with both RNA-dependent and DNA-dependent

polymerase A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using ba ...

functions, as well as an RNase H function. It acts on the HBV pre-genomic RNA (pgRNA) to reverse transcribe it to form a new rcDNA molecule within a new capsid. (The pgRNA has another function of being translated into the viral polymerase and core proteins). HBV core protein dimers are required for packaging of the pgRNA/polymerase complex. Then, after viral polymerase binds to the packaging signal (Hɛ) found at the 5′ end of the pgRNA, they are incorporated into the viral capsid. Inside the capsid, the pgRNA undergoes reverse transcription, which is initiated by protein priming at the tyrosine residue of the HBV polymerase. Thus, the (-) DNA strand is made. At the same time, the RNA template is degraded by the RNase H activity of the polymerase. A short RNA of about 15–18

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...

s at the 5′ end of the pgRNA (including the 5′ DR1 sequence) is not degraded and it is used as primer for (+) DNA strand synthesis. The resulting RC-DNA is partially double stranded. The (-) DNA strand is longer than a genome length, with a covalently bound polymerase and a redundant flap at the 5′ end. However, the (+) DNA strand synthesis is uncompleted by the polymerase, and there is a gap exists down to the 3′ end of the (+) DNA strand.

References

Viral nonstructural proteins Hepatitis B virus {{virus-stub