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. 2010 Aug 2;49(33):5731-3.
doi: 10.1002/anie.201000814.

RNA dynamics by design: biasing ensembles towards the ligand-bound state

Andrew C Stelzer  1 , Jeremy D Kratz, Qi Zhang, Hashim M Al-Hashimi
Affiliations

RNA dynamics by design: biasing ensembles towards the ligand-bound state

Andrew C Stelzer et al. Angew Chem Int Ed Engl. .
No abstract available

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Figures

Figure 1
Figure 1
Biasing the TAR dynamic structure ensemble toward an ARG-bound state. a) Design of the TARGC sequence based on the structural dynamics of the TAR and TAR-ARG complexes. ‘X-Y’ base pairs denote alternating A-U/U-A or G-C/C-G base pairs used in the elongation.[8,9] Residues undergoing the largest chemical shift perturbations due to the G-C mutation are highlighted in orange on the TARGC secondary structure. b) Representative 2D CH HSQC spectra of TAR (black), TARGC (orange), and TAR-ARG (purple). Inset: 2D C,H HSQC C5-H5 spectra. c,d) Correlation plots. Red: residues in helix I, green: helix II, orange: in the bulge. R = correlation coefficients. ■ C2-H2, ▼ C8-H8, ▲ C6-H6, &25cf C5-H5, ◆ C1’-H1’, ◀ N1/3-H1/3. c) Correlation plots between RDCs measured in non-elongated TAR, TARGC, and TAR-ARG complexes. d) Correlation plots between normalized resonance intensities measured in EI-TAR, EI-TARGC, and EI-TAR-ARG.
Figure 2
Figure 2
Interhelical structural dynamics of EI-TAR, EI-TARG22C40, and EI-TAR-ARG from order tensor analysis of RDCs measured in helix I elongated constructs. There are no constraints on rotations around the elongated axis.
Figure 3
Figure 3
TAR and TARGC converge to a common ARG-bound conformation. a) Representative 2D C,H HSQC spectra of TAR-ARG (green) and TARGC-ARG (purple). Inset: 2D HSQC C5-H5 spectra. b) Correlation plots between RDCs measured in TARGC, TARGC-ARG, and TAR-ARG. For symbol and color key, see Figure 1 c. c) Representative ARG titration curves for TAR (purple) and TARGC (green) as a function of total ARG concentration. Individual Kd values: top: G22 (TARGC) 96.6 ± 16.1 μm, A22 (TAR) 141 ± 13.2 μm; middle: U23 (TARGC) 31.3 ± 3.24 μm, U23 (TAR) 116 ± 16.1 μm; bottom: G28 (TARGC) 311 ± 65.1 μm, G28 (TAR) 414 ± 10.3 μm. Global Kd values: TARGC 47.7 ± 9.3 μm, TAR 140 ± 9.0 μm. d) TAR and TARGC adopt distinct unbound dynamic structure ensembles that converge to a common ARG-bound state. e) Representative 2D C,H HSQC spectra of TAR-NEOB (red) and TARGC-NEOB (blue) with the chemical structure of NEOB shown.
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