Cytohesin-2 aptamer

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Timeline

2004

Mirko G Theis et.al selected and applied a specific inhibitor for ARF nucleotide-binding site opener (ARNO)/cytohesin-2[1]

2009

Mayer G et.al describe a general route starting with the de novo selection process targeting cytohesin-1 and aiming at the synthesis of caged aptamers[2]

2013

Niebel B et.al had identified three aptamers sharing a 15 nucleotides consensus motif, which were specifically target Tiam1[3]

Description

 In 2004，Theis M.G and Knorre A had used an in Vitro Selectionan to isolate RNA aptamers with high affinity for cytohesin-2. This aptamer bound to an N-terminal segment of cytohesin-2 and did not inhibit ARF-GEF function in vitro[1].

SELEX

In 2004, Theis MG and colleagues used existing research to design the method required for the in vitro genetic-selection. Starting from a RNA pool that had a sequence of 40 random nucleotide positions, aptamers that bind specifically to cytohesin-2 were selected after 15 rounds of selection and amplification. The aptamer, K61, can bind specifically to cytohesin-2 were selected with high affinity[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[1].

5'-GGGAGAGACAAGCUUGGGUCGCGUUUUGCUAUUGAUGUUCUUUUAACCUGGCCUGUUUGGGCCUCUUGCUCUUCCUAGGAGU-3'

 drawing


Ligand information

SELEX ligand

Cytohesin-2 is a protein that in humans is encoded by the CYTH2 gene. Cytohesin-2 (CYTH2), formerly known as Pleckstrin homology, Sec7 and coiled/coil domains 2 (PSCD2), is a member of the cytohesin family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of CYTHs with membranes.-----From Wiki

Name Uniprot ID Pfam MW Amino acids sequences PDB Gene ID
Cytohesin-2 Q99418 PTHR10663 46.546 kDa MEDGVYEPPDLTPEERMELENIRRRKQELLVEIQRLREELSEAMSEVEGLEANEGSKTLQRNRKMAMGRKKFNMDPKKGIQFLVENELLQNTPEEIARFLYKGEGLNKTAIGDYLGEREELNLAVLHAFVDLHEFTDLNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCLCNPGVFQSTDTCYVLSFAVIMLNTSLHNPNVRDKPGLERFVAMNRGINEGGDLPEELLRNLYDSIRNEPFKIPEDDGNDLTHTFFNPDREGWLLKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVDDPRKPNCFELYIPNNKGQLIKACKTEADGRVVEGNHMVYRISAPTQEEKDEWIKSIQAAVSVDPFYEMLAARKKRISVKKKQEQP 1PBV 9266

The aptamer bind to the affinity of the protein.

Name Sequence Ligand Affinity
K61_aptamer 5'-GGGAGAGACAAGCUUGGGUCGCGUUUUGCUAUUGAUGUUCUUUUAACCUGGCCUGUUUGGGCCUCUUGCUCUUCCUAGGAGU-3' cytohesin-2 115 ± 3 nM
K61_aptamer 5'-GGGAGAGACAAGCUUGGGUCGCGUUUUGCUAUUGAUGUUCUUUUAACCUGGCCUGUUUGGGCCUCUUGCUCUUCCUAGGAGU-3' cytohesin-1 4000 nM
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
6BBP-A 27.9 2.1 Cytohesin-3, Adp-Ribosylation Factor 6
8UCQ-A 24.7 1.3 Sec7 Domain-Containing Protein
7VMB-A 22.3 2.1 Iq Motif And Sec7 Domain-Containing Protein 1
1XSZ-A 19.5 2.5 Guanine Nucleotide Exchange Protein
8EZJ-A 17.2 2.3 Arf Guanine-Nucleotide Exchange Factor 2
5L7S-A 5.2 3.6 Secreted Rxlr Effector Peptide Protein
7V99-A 4.4 4.4 Telomerase Reverse Transcriptase
7XVK-B 4.1 3.9 Serine/Threonine-Protein Phosphatase 2A 65 Kda Re
8UMD-B 4.1 11.3 Flagellar M-Ring Protein
4J8S-A 4.0 4.4 Ccr4-Not Transcription Complex Subunit 1


References

[1] Discriminatory aptamer reveals serum response element transcription regulated by cytohesin-2.
Theis MG, Knorre A, Kellersch B, Moelleken J, Wieland F, Kolanus W, Famulok M.
Proc Natl Acad Sci U S A. 101(31):11221-6. (2004)
[2] From selection to caged aptamers: identification of light-dependent ssDNA aptamers targeting cytohesin.
Mayer G, Lohberger A, Butzen S, Pofahl M, Blind M, Heckel A.
Bioorg Med Chem Lett. 19(23):6561-4. (2009)
[3] RNA-aptamers that modulate the RhoGEF activity of Tiam1.
Niebel B, Wosnitza CI, Famulok M.
Bioorg Med Chem. 21(20):6239-46. (2013)