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Binding of an RNA aptamer and a partial peptide of a prion protein: crucial importance of water entropy in molecular recognition.

Hayashi T, Oshima H, Mashima T, Nagata T, Katahira M, Kinoshita M - Nucleic Acids Res. (2014)

Bottom Line: The energy decrease due to the gain of R12-P16 attractive (van der Waals and electrostatic) interactions is almost canceled out by the energy increase related to the loss of R12-water and P16-water attractive interactions.We can explain the general experimental result that stacking of flat moieties, hydrogen bonding and molecular-shape and electrostatic complementarities are frequently observed in the complexes.It is argued that the water-entropy gain is largely influenced by the geometric characteristics (overall shapes, sizes and detailed polyatomic structures) of the biomolecules.

View Article: PubMed Central - PubMed

Affiliation: Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan.

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Structural images of the upper half of the R12:P16 complex. It is taken from an NMR structure (model 1) constructed as described in ‘Structure Modeling for R12:P16 Complex’. R12 and P16 are drawn on the upper and lower sides, respectively, using the space-filled model. (a) Contact of a phosphate group in R12 with a lysine residue in P16. The phosphate backbone (C5′-C4′-C3′-PO4−) and Lys8 are depicted by the licorice model. (b) π–π stacking of a guanine nucleotide in R12 and an indole ring of tryptophan in P16. The quadruplex tetrad plane containing G:G:G:G (G denotes a guanine nucleotide) and Trp3 are depicted by the licorice model. The water molecules are omitted here. This figure is drawn using the VMD
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Figure 2: Structural images of the upper half of the R12:P16 complex. It is taken from an NMR structure (model 1) constructed as described in ‘Structure Modeling for R12:P16 Complex’. R12 and P16 are drawn on the upper and lower sides, respectively, using the space-filled model. (a) Contact of a phosphate group in R12 with a lysine residue in P16. The phosphate backbone (C5′-C4′-C3′-PO4−) and Lys8 are depicted by the licorice model. (b) π–π stacking of a guanine nucleotide in R12 and an indole ring of tryptophan in P16. The quadruplex tetrad plane containing G:G:G:G (G denotes a guanine nucleotide) and Trp3 are depicted by the licorice model. The water molecules are omitted here. This figure is drawn using the VMD

Mentions: The clue to the molecular-recognition mechanism is the driving force for the binding. The force has been investigated primarily from the viewpoint of structural biology on the basis of the three-dimensional (3D) structure of the aptamer–target complex. A prevailing view is that an aptamer binds to its targets via aptamer–target electrostatic attractive interactions due to the contact of groups with positive and negative charges, that is, the electrostatic complementarity. Actually, in several aptamer–target complexes, negatively charged phosphate backbones in the aptamer are in contact with positively charged moieties of the targets. For example, Toggle-25t (an RNA aptamer) binds to the positively charged arginine-rich surface of thrombin (15). In the R12:P16 complex, the contact of phosphate groups of R12 with lysine residues of P16 is observed as illustrated in Figure 2 (5) (Figures 2, 4 and 5 are drawn using the Visual Molecular Dynamics (VMD)(24)). However, there is an experimental result that raises a doubt with respect to this view: in the complex of Apt8 (an RNA aptamer) binding to the Fc fragment of Human IgG1 (hFc1), the aptamer-bound area of hFc1 consists of a less-positively charged surface (16,25). In the case of the R12–P16 binding, a π–π stacking interaction between a guanine nucleotide in R12 and an indole ring of tryptophan in P16 (see Figure 2) has been proposed as another important driving force (5). Taken together, the structural data have shown that precise stacking of flat moieties, specific hydrogen bonding and electrostatic complementarity frequently occur in the complexes (2).


Binding of an RNA aptamer and a partial peptide of a prion protein: crucial importance of water entropy in molecular recognition.

Hayashi T, Oshima H, Mashima T, Nagata T, Katahira M, Kinoshita M - Nucleic Acids Res. (2014)

Structural images of the upper half of the R12:P16 complex. It is taken from an NMR structure (model 1) constructed as described in ‘Structure Modeling for R12:P16 Complex’. R12 and P16 are drawn on the upper and lower sides, respectively, using the space-filled model. (a) Contact of a phosphate group in R12 with a lysine residue in P16. The phosphate backbone (C5′-C4′-C3′-PO4−) and Lys8 are depicted by the licorice model. (b) π–π stacking of a guanine nucleotide in R12 and an indole ring of tryptophan in P16. The quadruplex tetrad plane containing G:G:G:G (G denotes a guanine nucleotide) and Trp3 are depicted by the licorice model. The water molecules are omitted here. This figure is drawn using the VMD
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Related In: Results  -  Collection

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Figure 2: Structural images of the upper half of the R12:P16 complex. It is taken from an NMR structure (model 1) constructed as described in ‘Structure Modeling for R12:P16 Complex’. R12 and P16 are drawn on the upper and lower sides, respectively, using the space-filled model. (a) Contact of a phosphate group in R12 with a lysine residue in P16. The phosphate backbone (C5′-C4′-C3′-PO4−) and Lys8 are depicted by the licorice model. (b) π–π stacking of a guanine nucleotide in R12 and an indole ring of tryptophan in P16. The quadruplex tetrad plane containing G:G:G:G (G denotes a guanine nucleotide) and Trp3 are depicted by the licorice model. The water molecules are omitted here. This figure is drawn using the VMD
Mentions: The clue to the molecular-recognition mechanism is the driving force for the binding. The force has been investigated primarily from the viewpoint of structural biology on the basis of the three-dimensional (3D) structure of the aptamer–target complex. A prevailing view is that an aptamer binds to its targets via aptamer–target electrostatic attractive interactions due to the contact of groups with positive and negative charges, that is, the electrostatic complementarity. Actually, in several aptamer–target complexes, negatively charged phosphate backbones in the aptamer are in contact with positively charged moieties of the targets. For example, Toggle-25t (an RNA aptamer) binds to the positively charged arginine-rich surface of thrombin (15). In the R12:P16 complex, the contact of phosphate groups of R12 with lysine residues of P16 is observed as illustrated in Figure 2 (5) (Figures 2, 4 and 5 are drawn using the Visual Molecular Dynamics (VMD)(24)). However, there is an experimental result that raises a doubt with respect to this view: in the complex of Apt8 (an RNA aptamer) binding to the Fc fragment of Human IgG1 (hFc1), the aptamer-bound area of hFc1 consists of a less-positively charged surface (16,25). In the case of the R12–P16 binding, a π–π stacking interaction between a guanine nucleotide in R12 and an indole ring of tryptophan in P16 (see Figure 2) has been proposed as another important driving force (5). Taken together, the structural data have shown that precise stacking of flat moieties, specific hydrogen bonding and electrostatic complementarity frequently occur in the complexes (2).

Bottom Line: The energy decrease due to the gain of R12-P16 attractive (van der Waals and electrostatic) interactions is almost canceled out by the energy increase related to the loss of R12-water and P16-water attractive interactions.We can explain the general experimental result that stacking of flat moieties, hydrogen bonding and molecular-shape and electrostatic complementarities are frequently observed in the complexes.It is argued that the water-entropy gain is largely influenced by the geometric characteristics (overall shapes, sizes and detailed polyatomic structures) of the biomolecules.

View Article: PubMed Central - PubMed

Affiliation: Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan.

Show MeSH