7DD6
Structure of Ca2+/L-Trp-bonnd Calcium-Sensing Receptor in active state
Summary for 7DD6
| Entry DOI | 10.2210/pdb7dd6/pdb |
| EMDB information | 30645 |
| Descriptor | Calcium-sensing Receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | calcium-sensing receptor, casr, active state, membrane protein |
| Biological source | Gallus gallus (Chicken) |
| Total number of polymer chains | 2 |
| Total formula weight | 242373.14 |
| Authors | Wen, T.L.,Yang, X.,Shen, Y.Q. (deposition date: 2020-10-27, release date: 2021-06-16, Last modification date: 2024-10-09) |
| Primary citation | Wen, T.,Wang, Z.,Chen, X.,Ren, Y.,Lu, X.,Xing, Y.,Lu, J.,Chang, S.,Zhang, X.,Shen, Y.,Yang, X. Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor. Sci Adv, 7:-, 2021 Cited by PubMed Abstract: Calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) that plays an important role in calcium homeostasis and parathyroid hormone secretion. Here, we present multiple cryo-electron microscopy structures of full-length CaSR in distinct ligand-bound states. Ligands (Ca and l-tryptophan) bind to the extracellular domain of CaSR and induce large-scale conformational changes, leading to the closure of two heptahelical transmembrane domains (7TMDs) for activation. The positive modulator (evocalcet) and the negative allosteric modulator (NPS-2143) occupy the similar binding pocket in 7TMD. The binding of NPS-2143 causes a considerable rearrangement of two 7TMDs, forming an inactivated TM6/TM6 interface. Moreover, a total of 305 disease-causing missense mutations of CaSR have been mapped to the structure in the active state, creating hotspot maps of five clinical endocrine disorders. Our results provide a structural framework for understanding the activation, allosteric modulation mechanism, and disease therapy for class C GPCRs. PubMed: 34088669DOI: 10.1126/sciadv.abg1483 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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