Science Advances

Supplementary Materials

This PDF file includes:

  • table S1. Crystallographic statistics of hCaSR-ECD and hCaSR-ECD/Gd3+.
  • table S2. EC50 of Mg2+o for stimulation of Ca2+i signaling in the presence of different coactivators.
  • table S3. EC50 of Mg2+o for stimulation of Ca2+i signaling in cell population assay with or without TNCA.
  • table S4. EC50 of Mg2+o for stimulation of Ca2+i signaling in single cell assay with or without TNCA.
  • table S5. EC50 of Mg2+o-elicited Ca2+i responses in cell population assay with coapplication of various concentrations of TNCA.
  • fig. S1. Structure-based sequence alignment of CaSRs and mGluRs (by PROMALS3D).
  • fig. S2. Size exclusion chromatography of purified hCaSR-ECD.
  • fig. S3. Comparison of CaSR and mGluR2 structures.
  • fig. S4. CaSR-mediated ERK1/2 activation.
  • fig. S5. Ca2+i responses of CaSR stimulated by increasing Mg2+o.
  • fig. S6. Determining Mg2+ binding to hCaSR-ECD.
  • fig. S7. Metal binding at the acidic patch.
  • fig. S8. Identification of TNCA.
  • fig. S9. Determining TNCA binding capability to hCaSR-ECD.
  • fig. S10. Replacement of TNCA by phenylalanine.
  • fig. S11. Structural comparison of CaSRL binding site with that of mGluR1.
  • fig. S12. Disease-related mutations on CaSR ECD.
  • fig. S13. Structure of the proposed calcium binding site 1.
  • fig. S14. Identification of a bicarbonate anion near the ligand binding site.
  • fig. S15. A positively charged pocket for loop 1 association.
  • fig. S16. Identification of a potential Mg2+ binding site in the hinge region.

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