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, (? 12 ? 16H) Add 1mL of 500mM IPTG, and put the solution at around 20 ? C (to avoid protein aggregation) for 12 to 16 hours. After this step is completed, spin the cells down in polycarbonate tubes (? 7000g), get rid of the excess liquid, and freeze the pellet. The production process can be interrupted here

, Protein purification Resuspend cells into 50ml buffer A, add 100µL of 10mg/mL lysozyme and 1 protease inhibitor tablet (EDTA free)

, Freeze and thaw the solution three times

, Add 1mL of 1mg/mL DNase, 100µL of M gCl 2

, Wash with 50 mL of buffer A. Elute with 50 mL of buffer B. Run gel (12-15%) using the washing liquid and check the presence of your protein in the eluting solution, Load the supernatant onto Ni2+ column

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S. Figure, Fractional contact maps calculated from the pseudo free energy profile at 288 K. A-F correspond to the different Q value ranges defined in the Pseudo free energy profile in Figure S7. Grey dots correspond to the original contact map, colored dots correspond to the proportion of contact found in the given contact range, color code is given by the color scale of p(i,j)

, Grey dashed lines represent the limits of each repeat in the protein primary sequence

S. Figure, Fractional contact maps calculated from the pseudo free energy profile at 298 K. A-F correspond to the different Q value ranges defined in the Pseudo free energy profile in Figure S8. Grey dots correspond to the original contact map, colored dots correspond to the proportion of contact found in the given contact range, color code is given by the color scale of p(i,j)

, Grey dashed lines represent the limits of each repeat in the protein primary sequence

M. Dellarole, Royer 1,c * and Christian Roumestand 1 * Supplementary Material Supplementary Figure 3 Thermal dependences of pressure induced unfolding of A) the ultrastable ?+PHS protein (grey) and the single mutants B) L125A (red) and C) I92A (green) and D) the corresponding double mutant L125/I92A (orange) as followed by 2D 15 N-1 H HSQC. First column: normalized intensity profiles of individual amides as a function of pressure. Second column: histogram of single residue ?V f values derived from two-state unfolding model fit to intensity profiles. Under equilibrium conditions, native cross-peak intensities were integrated from the corresponding HSQC spectrum and the resulting intensity versus pressure data points were individually fitted for each resonance. The fitting procedure was equivalent to the one used for the high-pressure fluorescence experiments described in Figure S4, except no correction for quantum yield was applied. Experiments were recorded, and L125/I92A respectively. Fitting ?V f errors bars are shown as thin black lines

A. D+phs, , p.202

, fluorescence (black circles) and PPC (blue circle) Red line is a quadratic fit to ?V NMR and ?V PPC data. Black line is a quadratic fit to ?V fluorescence and ?V PPC data. Grey lines are linear fits to single residue ?V NMR data. PPC experiments were carried out in 10 mM Phosphate buffer pH 5.5. Fluorescence experiments were carried out in 10 mM Bis-tris ph 5

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