The intrinsic flexibility of the aptamer targeting the ribosomal protein S8 is a key factor for the molecular recognition

• Published in: Biochimica et biophysica acta Vol. 1862; no. 4; pp. 1006 - 1016
• Main Authors: Autiero, Ida, Ruvo, Menotti, Improta, Roberto, Vitagliano, Luigi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2018
• Subjects: Aptamer conformational flexibility; Molecular dynamics; Population shift mechanism; Protein-nucleic acid recognition; Ribosomal proteins; Population shift mechanism; IL; APT; H-bonds; Molecular dynamics; RMSD; Aptamer conformational flexibility; PDB; 400APTbound; Ribosomal proteins; APTbound; MD; RMSIP; TL; APT-S8compl; APTfree; Protein-nucleic acid recognition; APTbound/free; SELEX
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2018.01.014

Aptamers are RNA/DNA biomolecules representing an emerging class of protein interactors and regulators. Despite the growing interest in these molecules, current understanding of chemical-physical basis of their target recognition is limited. Recently, the characterization of the aptamer targeting the protein-S8 has suggested that flexibility plays important functional roles. We investigated the structural versatility of the S8-aptamer by molecular dynamics simulations. Five different simulations have been conducted by varying starting structures and temperatures. The simulation of S8-aptamer complex provides a dynamic view of the contacts occurring at the complex interface. The simulation of the aptamer in ligand-free state indicates that its central region is intrinsically endowed with a remarkable flexibility. Nevertheless, none of the trajectory structures adopts the structure observed in the S8-aptamer complex. The aptamer ligand-bound is very rigid in the simulation carried out at 300 K. A structural transition of this state, providing insights into the aptamer-protein recognition process, is observed in a simulation carried out at 400 K. These data indicate that a key event in the binding is linked to the widening of the central region of the aptamer. Particularly relevant is switch of the A26 base from its ligand-free state to a location that allows the G13-C28 base-pairing. Intrinsic flexibility of the aptamer is essential for partner recognition. Present data indicate that S8 recognizes the aptamer through an induced-fit rather than a population-shift mechanism. The present study provides deeper understanding of the structural basis of the structural versatility of aptamers. •The intrinsic plasticity of the S8 aptamer is essential for partner recognition.•The protein-aptamer recognition occurs through a population shift mechanism.•The aptamer binding is driven by charged interactions and movements of the A26 base.•Present findings suggests that malleability may be a recurrent property of aptamers.