An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription.
The T3 motif on the duck hepatitis B virus reverse transcriptase (P) is proposed to be a binding site essential for viral replication, but its ligand and roles in DNA synthesis are unknown. Here, we found that T3 is needed for P to bind the viral RNA, the first step in DNA synthesis. A second motif, RT-1, was predicted to assist T3. T3 and RT-1 appear to form a composite RNA binding site because mutating T3 and RT-1 had similar effects on RNA binding, exposure of antibody epitopes on P, and DNA synthesis. The T3 and RT-1 motifs bound RNA non-specifically, yet they were essential for specific interactions between P and the viral RNA. This implies that specificity for the viral RNA is provided by a post-binding step. The T3:RT-1 motifs are conserved with the human hepatitis B virus and may be an attractive target for novel antiviral drug development.
Badtke
Matthew P
MP
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
Khan
Irfan
I
Cao
Feng
F
Hu
Jianming
J
Tavis
John E
JE
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015613:Hepadnaviridae / Q000235:genetics* / Q000378:metabolism*; D015611:Hepatitis B Virus, Duck / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D048348:Reverse Transcription; D017386:Sequence Homology, Amino Acid
D018832:Molecular Chaperones; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase