No.21 aptamer

Jun 5, 2024 • Yuxuan Sun, Baowei Huang

Timeline

Description

In 2003, Akihiro Oguro and Takashi Ohtsu had used the SELEX methodology to select RNA aptamers with high affinity for eIF4A by in vitro RNA selection-amplification^[1].

SELEX

In 2003, Akihiro Oguro and colleagues used SELEX. Four RNA selection experiments were performed using fulllength eIF4A and RNA pools of either 30 or 40 random nucleotide positions. Then, from each selection, 48 RNA sequences were cloned, aptamers that bind specifically to eIF4A were selected with high affinity^[1].
Detailed information are accessible on SELEX page.

Structure

The 2D structure of the figures is based on the article by ribodraw tool to draw^[1].

5'-GGGAGACAAGAAUAAACGCUCAAGGGGACCGCGCCCCACAUGUGAGUGAGGCCGAAACAUAGAUUCGACAGGAGGCUCACAACAGGC-3'

Ligand information

SELEX ligand

The DEAD-box helicase domain found in eIF4A and related proteins are DEAD-box helicases, a diverse family of proteins involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. Eukaryotic initiation factor 4A-I (DDX2A) is involved in cap recognition and is required for mRNA binding to ribosome. This domain contains the ATP-binding region.-----From Pfam

Name	Uniprot ID	Pfam	MW	Amino acids sequences	PDB	Gene ID
eIF4A	P60842	IPR044728	46.154 kDA	MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLRGIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQIELDLKATQALVLAPTRELAQQIQKVVMALGDYMGASCHACIGGTNVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDEADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFMRDPIRILVKKEELTLEGIRQFYINVEREEWKLDTLCDLYETLTITQAVIFINTRRKVDWLTEKMHARDFTVSAMHGDMDQKERDVIMREFRSGSSRVLITTDLLARGIDVQQVSLVINYDLPTNRENYIHRIGRGGRFGRKGVAINMVTEEDKRTLRDIETFYNTSIEEMPLNVADLI	2G9N	1973

Some isolated sequences bind to the affinity of the protein.

Name	Sequence	Ligand	Affinity
no.21 aptamer	5'-GGGAGACAAGAAUAAACGCUCAAGGGGACCGCGCCCCACAUGUGAGUGAGGCCGAAACAUAGAUUCGACAGGAGGCUCACAACAGGC-3'	eIF4A	27nM
#11 aptamer	5'-GGGAGACAAGAAUAAAACGCUCAAACAUUGCAUCGACAGCUGCAAGGCUCCCGCCGUACAAACCUUCGACAGGAGGCUCACAACAGGC-3'	eIF4A	8 μM
#1 aptamer	5'-GGGAGACAAGAAUAAACGCUCAACAGGCGUUUAGCCUCUAAGUAACAGGGGCCUCCCAUGAGCUUCGACAGGAGGCUCACAACAGGC-3'	eIF4A	3 μM
#20 aptamer	5'-GGGAGACAAGAAUAAACGCUCAAGGGGACCGCGCCCCACAUGUGAGUGAGGCCGAAACGUAGAUUCGACAGGAGGCUCACAACAGGC-3'	eIF4A	44 nM
#30 aptamer	5'-GGGAGACAAGAAUAAACGCUCAAUGUGGAUGAUUUGUAUGAUCGCGCAUACAAUUCGACAGGAGGCUCACAACAGGC-3'	eIF4A	1 μM

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
8RC0-D	27.8	1.9	Cd2 Antigen Cytoplasmic Tail-Binding Protein 2
3I5X-A	25.0	2.3	Atp-Dependent Rna Helicase Mss116
7NAD-X	23.3	1.9	25S Rrna
6ZNP-A	19.1	2.7	Uncharacterized Atp-Dependent Helicase Ypra
5V9X-A	18.8	2.7	Atp-Dependent Dna Helicase
8VX9-B	18.5	2.9	Hama
4CGZ-A	18.0	2.8	Bloom'S Syndrome Helicase
1WP9-A	17.9	2.6	Atp-Dependent Rna Helicase, Putative
5DCA-A	17.2	2.6	Pre-Mrna-Splicing Helicase Brr2
2OCA-A	16.7	3.3	Atp-Dependent Dna Helicase Uvsw

References

[1] RNA aptamers to initiation factor 4A helicase hinder cap-dependent translation by blocking ATP hydrolysis.
Oguro A, Ohtsu T, Svitkin YV, Sonenberg N, Nakamura Y.
RNA. 9(4):394-407. (2003)
[2] RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes.
Miyakawa S, Oguro A, Ohtsu T, Imataka H, Sonenberg N, Nakamura Y.
RNA. 12(10):1825-34. (2006)