HIV-1 PR aptamer

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Description

In 2015, Prasad, V. R et al. isolated several RNA aptamers targeting the human immunodeficiency virus type 1 (HIV-1) protease (PR) using a method called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The function of these aptamers is to bind to HIV-1 PR, inhibit its activity, and thus prevent the replication cycle of the HIV virus. Research has shown that these RNA aptamers have high affinity and specificity, and can non competitively inhibit the protease activity of HIV-1 PR. Through further mutation analysis, researchers identified the secondary structural elements of the ligands crucial for PR binding and demonstrated their ability to inhibit HIV replication in vitro[1].



SELEX

In 2015, Prasad, V. R et al. used an RNA library of 1014 unique species to isolated aptamers. They improved binding to HIV-1 PR via nine SELEX rounds. After the 10th round, sequencing of 48 clones revealed four sequence families. To enhance the first generation RNA aptamers' binding affinity, they screened variants from a partially randomised pool and performed eight more selection rounds. Several variants were found in the 8th round pool of PR10.1 and PR10.9 RNA aptamers. These second-generation PR RNA aptamers exhibited significantly improved binding affinity. Through site-specific mutation analysis, researchers studied the predicted secondary structure of the second-generation PR10.1-8E RNA aptamer to identify key structural elements for PR binding[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. PR10.1-8E aptamer binds to HIV-1 aspartyl protease (PR)[1].

5'-GGGUUACCUAGGAGGAGAUGCUCUUAAGUGUAACUUCUCAUAACAUCCGGAGGCUUUUACUUCCGGGGACCUAAGUGACGUCUGAACUGCUUCGAA-3'

drawing


Ligand information

SELEX ligand

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

Name Sequence Ligand Affinity
PR10.1-8E 5'-GGGUUACCUAGGAGGAGAUGCUCUUAAGUGUAACUUCUCAUAACAUCCGGAGGCUUUUACUUCCGGGGACCUAAGUGACGUCUGAACUGCUUCGAA-3' HIV-1 protease (PR) 17 ± 3 nM
PR10.1-8A 5'-GGGUUACCUAGGAGGAGAUGCUCUUAAGUGUAACUUCUCGUAAUUCCCAAGGCUUUUACCUCGGGGUCCUAAGUGACGUCUGAACUGCUUCGAA-3' HIV-1 protease (PR) 2.2 ± 0.2 nM
PR10.1 5'-GGGUUACCUAGGAGGAGAUGCUCUUCAUUGUAACUUCUCAUAAUUUCCCGAGGCUUUUACUUUCGGGGUCCUAAGUGACGUCUGAACUGCUUCGAA-3' HIV-1 protease (PR) 115 ± 22 nM
PR10.9 5'-GGGUUACCUAGGAGGAGAUGCUACAUUACCUAAGUAAGAUUACGGCUUCGAGUUUAGAGACCUCUCCCUGGUAAGUGACGUCUGAACUGCUUCGAA-3' HIV-1 protease (PR) 93 ± 19 nM
PR10.9-8N 5'-GGGUUACCUAGGAGGAGAUGCUUUGACCUAAGGUAAGAUAACGGCUUCGAGUUCAGAGACCUCGCCCUGGUAAGUGACGUCUGAACUGCUUCGAA-3' HIV-1 protease (PR) 4.3 ± 0.2 nM
drawing

Structure ligand

Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4 T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity).-----From Uniprot

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
HIV-1 protease (PR) P03366 PF00077 10.792 kDa
...... PQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNF
4ZIP AH002345

Similar compound(s)

We used the Dail server website to compare the structural similarities of ligand proteins, and chose the top 10 in terms of similarity for presentation.

Dail server website: a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB).

Z-score: a standard score that is converted from an original score. The list of neighbours is sorted by Z-score. Similarities with a Z-score lower than 2 are spurious.

RMSD: (Root Mean Square Deviation) is used to measure the degree to which atoms deviate from the alignment position.

PDB: PDB ID+ chain name.

PDB Z-socre RMSD Description
4ZIP-A 23.2 0 Protease
5UOV-A 22.6 0.1 Protease
5UPZ-A 22.6 0.1 Protease
3DK1-A 22.6 0.1 Protease
3DJK-A 22.5 0.1 Protease
4KB9-B 22.5 0.1 Protease
3H5B-A 22.5 0.2 HIV-1 Protease
8FUI-A 22.5 0.1 Protease
6E9A-A 22.5 0.2 Protease
3ST5-A 22.4 0.2 Protease


References

[1] High-affinity RNA Aptamers Against the HIV-1 Protease Inhibit Both In Vitro Protease Activity and Late Events of Viral Replication.
Duclair, S., Gautam, A., Ellington, A., & Prasad, V. R.
Molecular therapy. Nucleic acids, 4(2), e228. (2015)