The protein calsenilin aptamer

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Timeline

2001

Dg Jo. et al. found that calsenilin is a protein that interacts with presenilin-2 to cause production of pathogenic Aβ42 in Alzheimer’s disease (AD)[1]

2001

M Osawa et al. found that the protein is active when calcium ion is bound to its EF-hand domain[2]

2002

Theodore A Craig et al. found that active conformation(s) of the protein is modulated by binding of Ca2+[3]

2003

Dong-Gyu Jo et al. found that increased intracellular calcium concentrations favor the active conformation, which induces neuronal apoptosis through interaction with the C-terminus of presenilin-2[4]

2004

Shibani Bhattacharya et al. found that in the case of calsenilin, calcium ion is the signaling agent. The signaling activity of this protein is then mediated by formation of this active conformation[5]

Description

 In 2007, Lee, K. H. et al.used the SELEX method to isolate the aptamer with high compatibility for the The protein calsenilin. As a functional protein, the biochemical role played by calsenilin may be a consequence of its different conformations. Intrinsically flexible proteins have several energetically degenerate conformations and the active conformation must be induced by binding of a signaling molecule. In the case of calsenilin, calcium ion is the signaling agent[6].

SELEX

In 2007, Lee, K. H. et al. carry out a standard SELEX technology using GST-fused calsenilin throughout the whole selection cycle. Since dimeric calsenilin adopts different conformations in the presence and absence of calcium, aptamer selections were independently carried out under both calcium-rich and calcium-free conditions. Selected RNA pools, obtained following 9 cycles of the SELEX procedure in the presence or absence of calcium ion, were cloned and sequenced[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[6].

5'-UUUAUGUAGGGAUGUAAGGGAUGGGCAAUGUGGCGA-3'

 drawing


Ligand information

SELEX ligand

Recoverin is a Ca(2+) -binding protein that controls phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase (GRK-1) in photoreceptor cells. It serves as a cancer-retina antigen that is expressed in retina and tumour cells and evokes antibodies and/or T cells in patients with cancer.-----From Pfam

Name Uniprot ID Pfam MW Amino acids sequences PDB Gene ID
The protein calsenilin Q9Y2W7 IPR028846 29.24 kDa MQPAKEVTKASDGSLLGDLGHTPLSKKEGIKWQRPRLSRQALMRCCLVKWILSSTAPQGSDSSDSELELSTVRHQPEGLDQLQAQTKFTKKELQSLYRGFKNECPTGLVDEDTFKLIYAQFFPQGDATTYAHFLFNAFDADGNGAIHFEDFVVGLSILLRGTVHEKLKWAFNLYDINKDGYITKEEMLAIMKSIYDMMGRHTYPILREDAPAEHVERFFEKMDRNQDGVVTIEEFLEACQKDENIMSSMQLFENVI 2JUL 30818

Some isolated sequences bind to the affinity of the protein.

Name Sequence Ligand Affinity
aptamer-2 5'-GGGACGCGUGGUACCGACGGAGGCUUGUUUAUGUAGGGAUGUAAGGGGAUGGGCAAUGUGGCGACAGCUUCCGCGGGGAUC-3' The protein calsenilin 43 nM for Ca2+ bound, 79 nM for Ca2+ unbound
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
1S1E-A 11.5 2.1 KV channel interacting protein 1
1FPW-A 11.0 2.3 Calcium-binding protein ncs-1
2R2I-A 10.9 2.1 Guanylyl cyclase-activating protein 1
2GGZ-A 10.8 2.0 Guanylyl cyclase-activating protein 3
2F2P-A 10.8 2.1 Calmodulin fused with calmodulin-binding domain o
1H4B-A 10.0 2.3 Polcalcin bet v 4
2N6A-A 9.9 2.2 Human calmodulin/connexin-36 peptide hybrid
1V1F-A 9.7 2.5 Calcineurin b-like protein 4
5X9A-B 9.6 2.6 Calaxin
4E53-A 9.6 2.2 Calmodulin, linker, iq motif of neuromodulin


References

[1] Pro-apoptotic function of calsenilin/DREAM/KChIP3.
Jo, D. G., Kim, M. J., Choi, Y. H., Kim, I. K., Song, Y. H., Woo, H. N., Chung, C. W., & Jung, Y. K.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 15(3), 589–591. (2001)
[2] Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing protein, calsenilin/DREAM/KChIP3.
Osawa, M., Tong, K. I., Lilliehook, C., Wasco, W., Buxbaum, J. D., Cheng, H. Y., Penninger, J. M., Ikura, M., & Ames, J. B.
The Journal of biological chemistry, 276(44), 41005–41013. (2001)
[3] The metal-binding properties of DREAM: evidence for calcium-mediated changes in DREAM structure.
Craig, T. A., Benson, L. M., Venyaminov, S. Y., Klimtchuk, E. S., Bajzer, Z., Prendergast, F. G., Naylor, S., & Kumar, R.
The Journal of biological chemistry, 277(13), 10955–10966. (2002)
[4] Contribution of presenilin/gamma-secretase to calsenilin-mediated apoptosis.
Jo, D. G., Chang, J. W., Hong, H. S., Mook-Jung, I., & Jung, Y. K.
Biochemical and biophysical research communications, 305(1), 62–66. (2003)
[5] Target selectivity in EF-hand calcium binding proteins.
Bhattacharya, S., Bunick, C. G., & Chazin, W. J.
Biochimica et biophysica acta, 1742(1-3), 69–79. (2004)
[6] An RNA aptamer that recognizes a specific conformation of the protein calsenilin.
Lee, K. H., Jeong, S., Yang, E. G., Park, Y. K., & Yu, J.
Bioorganic & medicinal chemistry, 15(24), 7545–7552. (2007)