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Hepatitis B virus DNA polymerase

From Wikipedia, the free encyclopedia

Hepatitis B viral protein
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
OrganismHepatitis B virus ayw/France/Tiollais/1979
SymbolP
UniProtP03156
Search for
StructuresSwiss-model
DomainsInterPro
Protein family
Protein P
Identifiers
Symbol?
InterProIPR037531
Available protein structures:
PDB  IPR037531  
AlphaFold

Hepatitis B virus DNA polymerase is ahepatitis Bviral protein.[1][2] It is aDNA polymerase that can use either DNA or RNA templates and aribonuclease H that cutsRNA in the duplex. Both functions are supplied by thereverse transcriptase (RT) domain.

Structure

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Thehepadnaviral P protein is organized into four domains: an N-terminal domain called the terminal protein (TP) (InterProIPR000201), a spacer domain which has no apparent function to the polymerase, a reverse transcriptase (RT) domain related to every otherreverse transcriptase domain, and a C-terminal Ribonuclease H (RNase H) domain (InterProIPR001462).

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

Function

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The Hepatitis B virus (HBV) polymerase is a multifunctionalenzyme, with both RNA-dependent and DNA-dependentpolymerase 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 andcore 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 the5′ 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 15–18nucleotides 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 the3′ end of the (+) DNA strand.[4]

References

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  1. ^Ono-Nita SK, Kato N, Shiratori Y, Masaki T, Lan KH, Carrilho FJ, Omata M (March 1999)."YMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: A study by in vitro full-length viral DNA transfection".Hepatology.29 (3):939–45.doi:10.1002/hep.510290340.PMID 10051501.
  2. ^Shaw T, Mok SS, Locarnini SA (November 1996)."Inhibition of hepatitis B virus DNA polymerase by enantiomers of penciclovir triphosphate and metabolic basis for selective inhibition of HBV replication by penciclovir".Hepatology.24 (5):996–1002.doi:10.1002/hep.510240504.PMID 8903366.
  3. ^abcdMenéndez-Arias L, Álvarez M, Pacheco B (October 2014). "Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase: mechanism of action and resistance".Current Opinion in Virology.8:1–9.doi:10.1016/j.coviro.2014.04.005.PMID 24814823.
  4. ^abcYang HC, Kao JH (September 2014)."Persistence of hepatitis B virus covalently closed circular DNA in hepatocytes: molecular mechanisms and clinical significance".Emerging Microbes & Infections.3 (9): e64.doi:10.1038/emi.2014.64.PMC 4185362.PMID 26038757.
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Varidnaviria)
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