E2 aptamer

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Timeline

2000

Whereas the structure of the monomeric Ab peptide is almost a random coil, a b-sheet structure exists for the oligomeric Ab, indicating that the self-assembly of Abinduces the b-sheet structure[1]

2002

The small oligomeric Aβ, including amyloid-derived diffusible ligands (ADDLs) and a 56 kDa soluble amyloid-b assembly (Aβ*56), is thought to be toxic to neuronal cells[2]

2005

Ab peptides can form amyloid fibrils by self-assembly via several oligomeric states such as soluble small oligomers and protofibrils[3]

2006

The two predominant species of Aβ are composed of 40 and 42 amino acids, named Aβ1-40 and Aβ1-42, respectively[4]

2009

Transmission electron micrographs indicated that E2 can stop the fibrillization of Ab1-40. The selected RNA aptamer has potential as therapeutic agents for AD pathogenesis[5]

Description

 In 2009, Tsuyoshi Takahashi et al. used the SELEX method to isolate the aptamer with high compatibility for the Amyloid beta-peptide (Aβ). Transmission electron micrographs indicated that E2 can stop the fibrillization of Ab1-40. The selected RNA aptamer has potential as therapeutic agents for AD pathogenesis[5].

SELEX

In 2009, Tsuyoshi Takahashi et al. use a systematic evolution of ligands using the exponential enrichment (SELEX) procedure, and have constructed RNA aptamers that bind to Ab1-40 and inhibit aggregation[5].
Detailed information are accessible on SELEX page.



Structure

The 2D structure of the figure is based on the prediction results of the RNA fold website by ribodraw tool to draw.

5'-GGGAUGUUCUAGGCGGUUGAUGAUUUGGGGUGUCGGGCGAUUUUUAGGGUUGGGCCAGGCCGUCAUCCAGAGUAGCAUAAUUGAUCCGA-3'

 drawing


Ligand information

SELEX ligand

Amyloid-beta precursor protein (APP, or A4) is associated with Alzheimer's disease (AD), because one of its breakdown products, amyloid-beta (A-beta), aggregates to form amyloid or senile plaques. Mutations in APP or in proteins that process APP have been linked with early-onset, familial AD. Individuals with Down's syndrome carry an extra copy of chromosome 21, which contains the APP gene, and almost invariably develop amyloid plaques and Alzheimer's symptoms.-----From Pfam

Name Uniprot ID Pfam MW Amino acids sequences PDB Gene ID
Amyloid beta-peptide (Aβ) P05067 IPR008155 86.96 kDa MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN 7MRK 351

Some isolated sequences bind to the affinity of the protein.

Name Sequence Ligand Affinity
E2 5'-GGGAUGUUCUAGGCGGUUGAUGAUUUGGGGUGUCGGGCGAUUUUUAGGGUUGGGCCAGGCCGUCAUCCAGAGUAGCAUAAUUGAUCCGA-3' Amyloid beta-peptide (Aβ) 10.9 μM
drawing

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
4PWQ-A 26.2 0.9 Amyloid beta a4 protein
3KTM-B 26.0 0.6 Amyloid beta a4 protein
4PWQ-B 25.9 0.6 Amyloid beta a4 protein
3KTM-H 25.8 0.6 Amyloid beta a4 protein
3KTM-E 25.7 0.6 Amyloid beta a4 protein
3KTM-D 25.6 0.8 Amyloid beta a4 protein
7MRM-A 21.5 0.5 Fusion protein of chicken cntn3 fn1-fn2 domains a
7MQY-A 20.3 1.1 Fusion protein of cntn4 and aplp2
7MRN-C 19.7 1.0 Contactin-5
1MWP-A 19.2 1.2 Amyloid a4 protein


References

[1] Structural studies of soluble oligomers of the Alzheimer beta-amyloid peptide.
Huang, T. H., Yang, D. S., Plaskos, N. P., Go, S., Yip, C. M., Fraser, P. E., & Chakrabartty, A.
ournal of molecular biology, 297(1), 73–87. (2000)
[2] Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets.
Klein W. L.
Neurochemistry international, 41(5), 345–352. (2002)
[3] Fine structure study of Abeta1-42 fibrillogenesis with atomic force microscopy.
Arimon, M., Díez-Pérez, I., Kogan, M. J., Durany, N., Giralt, E., Sanz, F., & Fernàndez-Busquets, X.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 19(10), 1344–1346. (2005)
[4] High sensitivity analysis of amyloid-beta peptide composition in amyloid deposits from human and PS2APP mouse brain.
Güntert, A., Döbeli, H., & Bohrmann, B.
Neuroscience, 143(2), 461–475. (2006)
[5] RNA aptamers selected against amyloid beta-peptide (Abeta) inhibit the aggregation of Abeta.
Takahashi, T., Tada, K., & Mihara, H.
Molecular bioSystems, 5(9), 986–991. (2009)