Structural highlights
Publication Abstract from PubMedMucin 1 is a well-established target for early diagnosis of epithelial cancers. The nucleotides of the S1.3/S2.2 DNA aptamer involved in binding to VNTR (variable number tandem repeat) mucin 1 peptides have been identified with 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 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 VNTR peptides. The thermal dependence of NMR chemical shift data shows that the base-paired nucleotides melt cooperatively at 47 +/- 4 degrees C. The structure of the 25-mer oligonucleotide has been determined by 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 that are capped by a TTT triloop motif. The 3D model structures (PDB 2L5K) and BCE molecular models (Biopolymer Chain Elasticity) are consistent with both NMR and long unconstrained molecular dynamics (10 ns) in explicit water, respectively. Solution structure of a truncated anti-MUC1 DNA aptamer determined by mesoscale modeling and NMR.,Baouendi M, Cognet JA, Ferreira CS, Missailidis S, Coutant J, Piotto M, Hantz E, du Penhoat CH FEBS J. 2011 Nov 29. doi: 10.1111/j.1742-4658.2011.08440.x. PMID:22129448[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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