Fig. 5

Activations of VDRRXRα heterodimer with cognate VBS BGLAP and TRPV6 by selective modulator Cmpd3 verse natural ligand 1,25D3. Schematic representations illustrate differential experiments of ligand bound VDRRXRα heterodimer with respect to DNA and SRC1 RID binding (on the left). Differential consolidation HDX data are mapped onto the VDRRXR heterodimer structure model when the complex is bound to different ligands and DNA (shown in ribbon a−d), and SRC1 RID (shown in surface e−h) (on the right). Conformational changes of 1,25D3-bound heterodimer upon binding of a BGLAP VBS (Supplementary Fig. 1b, d, column (xvii)) and b TRPV6 VBS (Supplementary Fig. 1b, d, column (xviii)). Conformational changes of selective modulator Cmpd3 bound heterodimer upon binding of c BGLAP VBS (Supplementary Fig. 1b, d, column (xix)) and d TRPV6 VBS (Supplementary Fig. 1b, d, column (xx)). e Conformational changes of VDRRXRα: 1,25D3: BGLAP complex upon SRC1 RID binding (Supplementary Fig. 1b, d, column (xxi)). f Conformational changes of VDRRXRα: 1,25D3: TRPV6 complex upon SRC1 RID binding (Supplementary Fig. 1b, d, column (xxii)). g Conformational changes of VDRRXRα: Cmpd3: BGLAP complex upon SRC1 RID binding (Supplementary Fig. 1b, d, column (xxiii)). h Conformational changes of VDRRXRα: Cmpd3: TRPV6 complex upon SRC1 RID binding (Supplementary Fig. 1b, d, column (xxiv)). Percentages of deuterium differences are coded as Fig. 1. Dark gray, no statistically significant changes between compared conditions; light gray, regions that have no sequence coverage and include proline residue that has no amide hydrogen exchange activity; black, DNA VBSs; purple, 1,25D3 ligand; pink, Cmpd3. i Differential deuterium uptake plots of peptide aa411−419 from VDR H12 when heterodimer is bound to 1,25D3, DNA and SRC1 RID. j Differential deuterium uptake plots of peptide aa411−419 from VDR H12 when heterodimer is bound to Cmpd3, DNA, and SRC1 RID. The data are plotted as percent deuterium uptake verse time on a logarithmic scale