WL-2 aptamer

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Timeline

1985

The aggregation and deposition in vivo of β2-microglobulin (β2m) into amyloid fibrils occurs as a complication of long-term hemodialysis for end-stage renal failure leading to dialysis-related amyloidosis (DRA)[1]

1986

β2m normally forms the noncovalently bound light chain of the class I major histocompatability complex. As part of its normal catabolic cycle, β2m dissociates from the heavy chain of the class I major histocompatability complex that is displayed on the surface of all nucleated cells, whereupon it is carried in the plasma to the kidneys where it is filtered in the glomeruli and degraded in the proximal tubules[2]

1997

Although amyloid and amyloid-like fibrils are formed from diverse precursor proteins with unrelated primary sequences and tertiary folds, they all adopt a cross-β molecular architecture, identified by x-ray fiber diffraction[3]

2002

The ubiquitous ability of amyloid fibrils to bind serum amyloid P component, glycosaminoglycans and apolipoprotein E , together with the finding that antibodies raised against Aβ-(1-40) amyloid fibrils are also able to recognize amyloid fibrils formed from a wide variety of proteins and peptides[4]

2002

 RNA aptamers have already been generated against amyloid-like fibrils formed from Aβ-(1-40) [5]

Description

 In 2007, David H J Bunka et al. used the SELEX method to isolate the aptamer with high compatibility for the Amyloid-like fibrils formed in vitro from monomeric beta-2-microglobulin (β2m). WL-2 binds to WL and LS fibrils with an on-rate that is much faster than the binding of LS-5 to the same fibrillar targets , suggesting that although these aptamers recognize an epitope present in both WL and LS fibrils, the epitope for each aptamer must be either distinct or differentially accessible in the different fibril forms[6].

SELEX

In 2007, David H J Bunka et al. have exploited the power of RNA selection techniques to isolate small, structured, single-stranded RNA molecules known as aptamers that were targeted specifically to amyloid-like fibrils formed in vitro from beta(2)-microglobulin (beta(2)m), the amyloid fibril protein associated with dialysis-related amyloidosis[6].
Detailed information are accessible on SELEX page.



Structure

The 2D structure of the figure is based on the article by ribodraw tool to draw.

5'-GGGCCAAGCUUGCAUGCCUGCAGAAAAAUAAAGUGUGUACACUAAAUUGCUAGCCCCCGGAAAGAAGGUCAACAAAAGUCAGUGGUACCGAGCUCAGGUUCCC-3'

 drawing


Ligand information

SELEX ligand

β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells). In humans, the β2 microglobulin protein is encoded by the B2M gene.-----From Wiki

Name Uniprot ID Pfam MW Amino acids sequences PDB Gene ID
Amyloid-like fibrils formed in vitro from monomeric beta-2-microglobulin (β2m) P05067 IPR008155 86.96 kDa MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN NA 351

Some isolated sequences bind to the affinity of the protein.

Name Sequence Ligand Affinity
WL-2 5'-GGGCCAAGCUUGCAUGCCUGCAGAAAAAUAAAGUGUGUACACUAAAUUGCUAGCCCCCGGAAAGAAGGUCAACAAAAGUCAGUGGUACCGAGCUCAGGUUCCC-3' β2m Amyloid Fibril 7.48 nM
M-2 5'-GGGCCAAGCUUGCAUGCCUGCAGUUGGUUACGCGUACAGUGAAACUCGGAAAGUUGAAGGGCCAAAUGGGAACGGUACCGAGCUCAGGUUCCC-3' β2m Amyloid Fibril 11.5 nM
LS-5 5'-GGGCCAAGCUUGCAUGCCUGCAGGCAAACGGGGGCGUUUCGGCGGAGGAGUGGGAAGAAAAACGAGAGAAGAGUUGGAACGGGUACCGAGCUCAGGUUCCC-3' β2m Amyloid Fibril 22.1 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
6ZCF-A 5.4 0.0 Serum amyloid A-2 protein
6ZCF-L 5.2 0.1 Serum amyloid A-2 protein
6ZCG-V 5.0 0.6 Serum amyloid A-2 protein
6ZCG-W 5.0 0.6 Serum amyloid A-2 protein
6ZCG-F 5.0 0.6 Serum amyloid A-2 protein
6ZCG-J 4.9 0.6 Serum amyloid A-2 protein
6ZCG-C 4.9 0.6 Serum amyloid A-2 protein
6ZCG-B 4.9 0.6 Serum amyloid A-2 protein
6ZCG-T 4.7 0.8 Serum amyloid A-2 protein
6ZCG-L 4.7 0.8 Serum amyloid A-2 protein


References

[1]  new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin.
Gejyo, F., Yamada, T., Odani, S., Nakagawa, Y., Arakawa, M., Kunitomo, T., Kataoka, H., Suzuki, M., Hirasawa, Y., & Shirahama, T. 
Biochemical and biophysical research communications, 129(3), 701–706. (1985)
[2] Beta 2-microglobulin-associated amyloidosis in chronic haemodialysis patients.
Chanard, J., Lavaud, S., Toupance, O., Melin, J. P., Gillery, P., & Revillard, J. P.
Lancet (London, England), 1(8491), 1212. (1986)
[3] Common core structure of amyloid fibrils by synchrotron X-ray diffraction.
Sunde, M., Serpell, L. C., Bartlam, M., Fraser, P. E., Pepys, M. B., & Blake, C. C.
Journal of molecular biology, 273(3), 729–739.  (1997)
[4] Conformational Abs recognizing a generic amyloid fibril epitope.
O'Nuallain, B., & Wetzel, R.
Proceedings of the National Academy of Sciences of the United States of America, 99(3), 1485–1490. (2002)
[5] Selection of RNA aptamers to the Alzheimer's disease amyloid peptide.
Ylera, F., Lurz, R., Erdmann, V. A., & Fürste, J. P.
Biochemical and biophysical research communications, 290(5), 1583–1588. (2002)
[6] Production and characterization of RNA aptamers specific for amyloid fibril epitopes.
Bunka, D. H., Mantle, B. J., Morten, I. J., Tennent, G. A., Radford, S. E., & Stockley, P. G.
The Journal of biological chemistry, 282(47), 34500–34509. (2007)