Fig. 2: Ligand-induced hVDR conformational changes. | Nature Communications

Fig. 2: Ligand-induced hVDR conformational changes.

From: Cytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia

Fig. 2

a Differential deuterium uptake (ΔHDX) of hVDR between apo and ZK-bound (left panel) or 1,25D3-bound (right panel) hVDR/hRXRαΔNTD heterodimers. The VDR LBD is composed of H1–H12. Negative values indicate decreased deuterium incorporation upon ligand binding. Dashed lines represent a ΔHDX of 5%. b Average ΔHDX of hVDR between ZK-bound and apo-hVDR/hRXRαΔNTD heterodimers across the various time points mapped onto hVDR LBD (PDB: 1DB144). Regions not covered by HDX-MS are shown in dark gray. Differential deuterium uptake plots of the hVDR residues 414-LTPLVL-419 located in H12 (c) and of 152-QFRPPVR-158 located in the H1–H3 loop (d) determined in ZK-bound, 1,25D3-bound and apo hVDR/hRXRαΔNTD heterodimers. e Zoom of average ΔHDX across the various time points of the VDR region encompassing H2 and a nuclear localization signal (NLS) mapped onto the hVDR LBD (PDB: 1DB144). HDX-MS data were collected in triplicates, and deuteration data were normalized to the maximal theoretical uptake (±s.e.m.).

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