PMID: 27434672

 

    Legend: Gene, Sites

Title : Structural mechanism of ligand activation in human calcium-sensing receptor

Abstract :

1. Human calcium-sensing receptor ( CaSR ) is a G-protein-coupled receptor ( GPCR ) that maintains extracellular Ca(2 +) homeostasis through the regulation of parathyroid hormone secretion
2. It functions as a disulfide-tethered homodimer composed of three main domains , the Venus Flytrap module, cysteine-rich domain , and seven-helix transmembrane region
3. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations
4. We provide direct evidence that L-amino acids are agonists of the receptor
5. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation
6. Our structures reveal multiple binding sites for Ca(2 +) and PO4(3-) ions
7. Both ions are crucial for structural integrity of the receptor
8. While Ca(2 +) ions stabilize the active state, PO4(3-) ions reinforce the inactive conformation
9. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 3. CaSR, domain

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX