2L5K

Solution structure of truncated 23-mer DNA MUC1 aptamer

Summary for 2L5K

• Entry DOI: 10.2210/pdb2l5k/pdb
• Descriptor: DNA (5'-R(*(N68)P*G)-D(*CP*AP*GP*TP*TP*GP*AP*TP*CP*CP*TP*TP*TP*GP*GP*AP*TP*AP*CP*CP*CP*TP*GP*GP*T)-3') (1 entity in total)
• Functional Keywords: nmr solution structure, dyana and bce models, ttt triloop containing dna, truncated dna muc1 aptamer sequence, binding nucleotides, dna
• Total number of polymer chains: 1
• Total formula weight: 8164.29

Authors

Cognet, J.,Baouendi, M.,Hantz, E.,Missailidis, S.,Herve du Penhoat, C.,Piotto, M. (deposition date: 2010-11-02, release date: 2011-12-07, Last modification date: 2024-05-01)

Primary citation

Baouendi, M.,Cognet, J.A.,Ferreira, C.S.,Missailidis, S.,Coutant, J.,Piotto, M.,Hantz, E.,Herve du Penhoat, C.
Solution structure of a truncated anti-MUC1 DNA aptamer determined by mesoscale modeling and NMR.
Febs J., 279:479-490, 2012

PubMed Abstract: Mucin 1 is a well-established target for the early diagnosis of epithelial cancers. The nucleotides of the S1.3/S2.2 DNA aptamer involved in binding to variable number tandem repeat mucin 1 peptides have been identified using footprinting experiments. The majority of these binding nucleotides are located in the 25-nucleotide variable region of the total aptamer. Imino proton and 2D NMR spectra of truncated and total aptamers in supercooled water reveal common hydrogen-bonding networks and point to a similar secondary structure for this 25-mer sequence alone or embedded within the total aptamer. NMR titration experiments confirm that the TTT triloop structure is the primary binding site and show that the initial structure of the truncated aptamers is conserved upon interaction with variable number tandem repeat peptides. The thermal dependence of the NMR chemical shift data shows that the base-paired nucleotides melt cooperatively at 47 ± 4°C. The structure of the 25-mer oligonucleotide was determined using a new combined mesoscale molecular modeling, molecular dynamics and NMR spectroscopy investigation. It contains three Watson-Crick pairs, three consecutive mispairs and four Watson-Crick pairs capped by a TTT triloop motif. The 3D model structures (PDB 2L5K) and biopolymer chain elasticity molecular models are consistent with both NMR and long unconstrained molecular dynamics (10 ns) in explicit water, respectively. Database Structural data are available in the Protein Data Bank and BioMagResBank databases under the accession numbers 2L5K and 17129, respectively.

PubMed: 22129448
DOI: 10.1111/j.1742-4658.2011.08440.x

Experimental method

SOLUTION NMR