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1. Introduction
2. Class C G-Protein Coupled Receptors
3. Questions
4. Human GABAB receptor
5. GABAB receptor
6. GABABR functions as an obligatory heterodimer
7. GBR1:GBR2 ecodomain heterodimer structures
8. Apo structure
9. Antagonist-bound structures
10. Agonist-bound structures
11. Heterodimer interactions: resting & active states
12. Agonist-binding induced conformational changes
13. Ligand binding site
14. Chemical structures of agonists and antagonists
15. Antagonist-binding site: GBR1:GBR2 complex
16. Contacts between GBR1 & different antagonists
17. Contacts between GBR1 & different agonists
18. Ligand-binding site of the GBR1:GBR2 complex
19. Agonist vs. Antagonist binding (1)
20. Agonist vs. Antagonist binding (2)
21. LB1 mutations in the ligand-binding site
22. LB2 mutations in the ligand-binding site
23. Implications for receptor activation
24. GBR2 closure not needed for receptor activation
25. Disulfide-lined GABABR heterodimer: Design
26. Disulfide-lined GABABR heterodimer: Formation
27. Interfacrial disulfide locks GABABR in active state
28. Conformational equilibrium of GABAB receptor
29. Human calcium-sensing receptor
30. Extracellular calcium-sensing receptor
31. Diverse function of calcium-sensing receptor
32. Crystallization of deglycosylated CaSR
33. CaSR extracellular domain: Inactive structure
34. CaSR extracellular domain: Active structure
35. Homodimer Interactions: Inactive & Active States
36. L-amino acid recognition
37. L-amino acids are orthosteric agonists of CaSR
38. Common agonist-binding mode: Class C GPCRs
39. CaSR-mediated intracellular Ca2+ mobilization
40. Amino acids increase CaSR sensitivity to Ca2+
41. L-amino acid binding is required for CaSR activity
42. Ca2+ -binding sites
43. Identification of Ca2+-binding sites in CaSR
44. Ca2+ maintains the structural integrity of CaSR
45. Ca2+ stabilizes the active conformation of CaSR
46. L-amino Acids and Ca2+ are co-agonists of CaSR
47. Endogenous agonist of CaSR
48. Anion binding sites
49. Identification of anion-binding sites in CaSR
50. PO43- maintains the structural integrity of CaSR
51. PO43- negative modulatory effect: CaSR activity
52. Agonist-binding induced conformation changes
53. Activation of CaSR: An intricate interplay
54. Activation mechanism of class C GPCRs
55. Common activation mechanism of class C GPCRs
56. Acknowledgements

Topics Covered

• Crystal structures of human GABA(B) receptor extracellular domain in multiple functional states
• Agonist vs. antagonist recognition
• Identification of novel heterodimer interface associated with receptor activation
• Crystal structures of human CaSR in the inactive and active conformations
• Discovery of L-amino acids as orthosteric agonists of CaSR
• Identification of Ca2+ and PO43 binding sites in CaSR
• Universal activation mechanism of class C GPCRs

Links

Series:

• G Protein-Coupled Receptors (GPCRs) signaling in health and disease

Categories:

• Biochemistry
• Cell Biology

Talk Citation

Publication History

• Published on July 31, 2019

Financial Disclosures

• Dr. Qing R. Fan has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.