HIV-1 CA aptamer

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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, Lange, M. J et al. uesd the RNA library began with a randomised region consisting of 56 nucleotides (denoted as 56N), which was estimated to encompass approximately 1015 unique sequences. Through a meticulous screening process spanning 15 rounds, the CA15-2 RNA aptamer, capable of specifically binding to the CA lattice, was successfully identified. Subsequent analysis via Sanger sequencing technology revealed multiple cloned sequences, with CA15-2 being among the most prominent[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 aptamer binds to HIV-1 capsid (CA) protein. CA15-2 aptamer was named by Lange, M. J[1].

5'-GGAAGAAGAGAAUCAUACACAAGAUCGACGUACCUCAGGGUGGUGUAUGACUGAGGUGAAGACUGUGAACCAUGGCAUGCGGGCAUAAGGUAGGUAAGUCCAUA-3'

drawing


Ligand information

SELEX ligand

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

Name Sequence Ligand Affinity
CA15-2 5'-GGAAGAAGAGAAUCAUACACAAGAUCGACGUACCUCAGGGUGGUGUAUGACUGAGGUGAAGACUGUGAACCAUGGCAUGCGGGCAUAAGGUAGGUAAGUCCAUA-3' HIV-1 CA lattice 350 ± 50 nM (using MST at a CA protein concentration of 0.1 - 1000 nM),
502 ± 57 nM (using nitrocellulose filter binding assays at a CA protein concentration of 10-7500 nM)
drawing

Structure 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 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 capsid (CA) P12493 IPR045345 24.345 kDa
...... PIVQNLQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTHNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPGATLEEMMTAC
8FIU M19921

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 (Å) Description
8FIU-A 32.0 0 HIV-1 CAPSID
8FIU-C 30.4 0.5 HIV-1 CAPSID
7RMJ-A 29.4 1.3 CAPSID protein P24
7RJ4-A 29.3 1.3 CAPSID protein P24
6VKV-A 29.2 1.3 CAPSID protein P24
7RMJ-C 29.1 1.3 CAPSID protein P24
7RJ4-C 29.1 1.2 CAPSID protein P24
6VKV-C 29.1 1.2 CAPSID protein P24
7RAO-A 29.0 1.4 CAPSID protein P24
7RMM-A 28.9 0.7 CAPSID protein P24


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)