HBV P protein aptamer

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Description

In 2011, Hu, K. H et al. isolated aptamers targeting human hepatitis B virus (HBV) RNA packaging signals using the SELEX method. These aptamers can mimic the specific interaction between HBV polymerase (P protein) and the ε RNA stem ring structure on pgRNA, but do not support viral replication. Especially, the S9 aptamer has shown high affinity and specificity for recombinant truncated HBV P protein (miniP) in vitro experiments, and does not support viral replication when used as part of the complete HBV genome. Introducing S9 RNA into HepG2 cells that briefly produce HBV strongly inhibited the packaging and DNA synthesis of pgRNA, indicating that S9 RNA can act as an ε bait to competitively inhibit the binding of P protein to the real ε signal on pgRNA. This study demonstrates the successful identification of human HBV ε - aptamers using the in vitro SELEX method, and that S9 aptamers effectively inhibit HBV replication, providing a theoretical basis for the formation of ε - bait RNA interference virus P - ε complexes, and suggesting that S9 class RNA may be further developed as a useful therapeutic tool for chronic hepatitis B[1].



SELEX

In 2011, Hu, K. H et al. used an in-vitro reconstruction system based on recombinant truncated HBV P protein (miniP) to select potential e-structure aptamers from two large, randomised upper stem e-RNA pools. After three rounds of screening, these RNA pools were rich in RNAs with a strong affinity for miniPs. Around 500 RT-PCR product clones were generated, and 45 were randomly sequenced. Most (43) had upper stem sequences rich in adenosine (A). The selected adaptors, S6 and S9, showed high affinity and specificity for miniPs in vitro. Notably, S9 RNA effectively inhibited pgRNA packaging and DNA synthesis, suggesting it could act as a decoy for the e structure by competitively blocking the P protein’s binding to the authentic e signal on pgRNA[1].

Detailed information are accessible on SELEX page.



Structure

The 2D structure of the figure is based on the article by ribodraw tool to draw. S9 apatmer binds to hepatitis B virus (HBV) polymerase (P protein) (miniP). S9 aptamer was named by Hu, K. H et al[1].

5'-UGUUCAUGUCCUACUGUUCAAACAAAAAAACUGUGCACAAAAAUAAAUUGGGGCAUGGACA-3'

drawing

Ligand information

SELEX ligand

Some isolated sequences bind to the affinity of the protein[1].

Name Sequence Ligand Affinity
S9 5'-UGUUCAUGUCCUACUGUUCAAACAAAAAAACUGUGCACAAAAAUAAAUUGGGGCAUGGACA-3' HBV P protein NA

Structure ligand

This entry represents protein P from hepatitis B virus. Protein P is a multifunctional enzyme that converts the viral RNA genome into dsDNA in viral cytoplasmic capsids.-----From Pfam

UniProt ID: uniquely identifies protein sequences in the UniProt database, a resource for protein information.

Pfam: a widely recognised database of protein families and domains.

GenBank: maintained by NCBI(National Center for Biotechnology Information), is a database of nucleotide sequences from various organisms, vital for genetic and molecular biology research.

Mass: an intrinsic property of a body.

Name Uniprot ID Pfam Mass Protein sequence PDB ID GenBank
Hepatitis B virus (HBV) polymerase (P protein) (miniP) Q9QMN7 IPR037531 94.48 kDa
...... MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLYSSTVPVFNPDWQTPSFPHIHLKEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHIVNHYFQTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPGIRSQFKQSRLGLQPQQGSMASGTPGRSGIIRARVHSTTRQSFGVEPSGSGHIDSSTSSASSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELQHIPPSSTRSQSEGPILSCWWLQFRNSKPCSDYCLSHIVNLLEDWGPCTEYGEHHIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLPRYVARLSSXSRXINXQHXTMQBLHDSCSRNLYVSLXLLYKTXGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLDSLFTAVTNFLLSLGIHLNPTKTKRWGYTLNFMGYVIGSWGTLPQEHIVHKIKHCFRKLPINRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQAKQAFTFSPTYKAFLXXQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHQRMRGTFVXPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPADDPSRGRLGLYRPLLRLPYRPTTGRTSLYADSPSVPSHLPDRVHFASPLHVAWRPP
NA AB031265


References

[1] A SELEX-screened aptamer of human hepatitis B virus RNA encapsidation signal suppresses viral replication.
Feng, H., Beck, J., Nassal, M., & Hu, K. H.
PloS one, 6(11), e27862. (2011)