Hepatitis B virus DNA polymerase

Hepatitis B virus DNA polymerase is a hepatitis B viral protein.^[1][2] It is a DNA polymerase that can use either DNA or RNA templates and a ribonuclease H that cuts RNA in the duplex. Both functions are supplied by the reverse transcriptase (RT) domain.

Protein P (DNA polymerase / RNase H)
The genome organisation of HBV; the genes overlap. ORF P, in blue, encodes Hepatitis B virus DNA polymerase.
Identifiers
Organism	Hepatitis B virus ayw/France/Tiollais/1979
Symbol	P
UniProt	P03156
Search for Structures Swiss-model Domains InterPro

Protein P
Identifiers
Symbol	?
InterPro	IPR037531

Structure

The hepadnaviral P protein is organized into four domains: an N-terminal domain called the terminal protein (TP) (InterPro: IPR000201), a spacer domain which has no apparent function to the polymerase, a reverse transcriptase (RT) domain related to every other reverse transcriptase domain, and a C-terminal Ribonuclease H (RNase H) domain (InterPro: IPR001462).

Uniquely, the hepadnavirus terminal protein (TP) domain contains a tyrosine residue that serves as a primer for the synthesis of the (−) DNA strand.^[3]

Function

The Hepatitis B virus (HBV) polymerase is a multifunctional enzyme, with both RNA-dependent and DNA-dependent polymerase 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).^[3]

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.^[3][4]

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.^[4] At the same time, the RNA template is degraded by the RNase H activity of the polymerase. A short RNA of about 15–18 nucleotides 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.^[3]

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.^[4]