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HIV-1 CA-aptamer
Description
In 2022, Gruenke PR, Aneja R, Welbourn S, et al. selexed for an RNA aptamer called CA15-2. The function of this aptamer is to specifically bind to the capsid lattice structure of HIV-1 and inhibit virus replication. Research has shown that CA15-2 selectively binds to the CA lattice rather than the CA monomer or CA hexamer, indicating that it may target an interface that exists only on the CA lattice and is easily accessible. In addition, the expression of CA15-2 in virus producing cells can inhibit the replication of HIV-1, but not in target cells, indicating that it may bind to a biologically relevant and accessible site during virus production, which may not be reachable in the subsequent replication step or remain unchanged after binding to the aptamer. Importantly, CA15-2 is the first identified aptamer that can specifically recognize the HIV-1 CA lattice[1].SELEX
In 2022, the RNA library Gruenke PR, Aneja R, Welbourn S, et al. used started with a random region containing 56N (56 nucleotides, where N represents any nucleotide), estimated to contain approximately 1015 unique sequences. Through screening, the RNA aptamer CA15-2 that can specifically bind to the CA lattice was ultimately obtained from the 15th round of screening. Multiple cloned sequences were identified using Sanger sequencing technology, including CA15-2[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. CA15-2 aptamer binds to HIV-1 capsid (CA) protein[1].5'-GGAAGAAGAGAAUCAUACACAAGAUCGACGUACCUCAGGGUGGUGUAUGACUGAGGUGAAGACUGUGAACCAUGGCAUGCGGGCAUAAGGUAGGUAAGUCCAUA-3'
Ligand information
SELEX ligand
Coronavirus (CoV) nucleocapsid (N) proteins have 3 highly conserved domains. The N-terminal domain (NTD) (N1b), the C-terminal domain (CTD)(N2b) and the N3 region. The N1b and N2b domains from SARS CoV, infectious bronchitis virus (IBV), human CoV 229E and mouse hepatic virus (MHV) display similar topological organisations. N proteins form dimers, which are asymmetrically arranged into octamers via their N2b domains. Domains N1b and N2b are linked by another domain N2a that contains an SR-rich region in which phosphorylation of specific serine residues allows the N protein to associate with the RNA helicase DDX1 permitting template read-through, and enabling the transition from discontinuous transcription of subgenomic mRNAs (sgmRNAs) to continuous synthesis of longer sgmRNAs and genomic RNA (gRNA). It has been shown that N proteins interact with nonstructural protein 3 (NSP3) and thus are recruited to the replication-transcription complexes (RTCs).-----From Pfam
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| HIV-1 capsid (CA) | P12493 | NA | 24.345 kDa | PIVQNLQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTHNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPGATLEEMMTAC | 8FIU | M19921 |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| CA15-2 | 5'-GGAAGAAGAGAAUCAUACACAAGAUCGACGUACCUCAGGGUGGUGUAUGACUGAGGUGAAGACUGUGAACCAUGGCAUGCGGGCAUAAGGUAGGUAAGUCCAUA-3' | HIV-1 CA lattice | 350 ± 50 nM |
Similar compound
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. The Dali server is a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB). Z-score is 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) value is used to measure the degree to which atoms deviate from the alignment position.
| PDB | Z-socre | RMSD | Description |
|---|---|---|---|
| 7ASL-A | 19.6 | 11.0 | Gag protein |
| 1L6N-A | 19.1 | 3.2 | Gag polyprotein |
| 2XGU-A | 17.8 | 2.6 | Relik capsid N-terminal domain |
| 6HWX-A | 12.2 | 3.0 | Putative gag polyprotein |
| 8C9M-A | 10.7 | 6.2 | Gag protein |
| 5A9E-A | 9.3 | 8.4 | Deltambd gag protein |
| 6RWG-A | 8.4 | 3.0 | Gag polyprotein |
| 7LGA-D | 7.1 | 2.2 | Retrotransposon-derived protein peg10 |
| 1QRJ-A | 6.2 | 4.8 | Htlv-i capsid protein |
| 7ST9-E | 4.9 | 6.3 | Checkpoint protein rad24 |
References
[1] Selection and identification of an RNA aptamer that specifically binds the HIV-1 capsid lattice and inhibits viral replication.Gruenke, P. R., Aneja, R., Welbourn, S., Ukah, O. B., Sarafianos, S. G., Burke, D. H., & Lange, M. J.
Nucleic acids research, 50(3), 1701–1717. (2022)