Registration for a live webinar on 'Innovative Vaccines and Viral Pathogenesis: Insights from Recent Monkeypox Research' is now open.
See webinar detailsWe noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Class C G-Protein Coupled Receptors
- Questions
- Human GABAB receptor
- GABAB receptor
- GABABR functions as an obligatory heterodimer
- GBR1:GBR2 ecodomain heterodimer structures
- Apo structure
- Antagonist-bound structures
- Agonist-bound structures
- Heterodimer interactions: resting & active states
- Agonist-binding induced conformational changes
- Ligand binding site
- Chemical structures of agonists and antagonists
- Antagonist-binding site: GBR1:GBR2 complex
- Contacts between GBR1 & different antagonists
- Contacts between GBR1 & different agonists
- Ligand-binding site of the GBR1:GBR2 complex
- Agonist vs. Antagonist binding (1)
- Agonist vs. Antagonist binding (2)
- LB1 mutations in the ligand-binding site
- LB2 mutations in the ligand-binding site
- Implications for receptor activation
- GBR2 closure not needed for receptor activation
- Disulfide-lined GABABR heterodimer: Design
- Disulfide-lined GABABR heterodimer: Formation
- Interfacrial disulfide locks GABABR in active state
- Conformational equilibrium of GABAB receptor
- Human calcium-sensing receptor
- Extracellular calcium-sensing receptor
- Diverse function of calcium-sensing receptor
- Crystallization of deglycosylated CaSR
- CaSR extracellular domain: Inactive structure
- CaSR extracellular domain: Active structure
- Homodimer Interactions: Inactive & Active States
- L-amino acid recognition
- L-amino acids are orthosteric agonists of CaSR
- Common agonist-binding mode: Class C GPCRs
- CaSR-mediated intracellular Ca2+ mobilization
- Amino acids increase CaSR sensitivity to Ca2+
- L-amino acid binding is required for CaSR activity
- Ca2+ -binding sites
- Identification of Ca2+-binding sites in CaSR
- Ca2+ maintains the structural integrity of CaSR
- Ca2+ stabilizes the active conformation of CaSR
- L-amino Acids and Ca2+ are co-agonists of CaSR
- Endogenous agonist of CaSR
- Anion binding sites
- Identification of anion-binding sites in CaSR
- PO43- maintains the structural integrity of CaSR
- PO43- negative modulatory effect: CaSR activity
- Agonist-binding induced conformation changes
- Activation of CaSR: An intricate interplay
- Activation mechanism of class C GPCRs
- Common activation mechanism of class C GPCRs
- 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:
Categories:
Talk Citation
Fan, Q.R. (2019, July 31). Extracellular domain structures from calcium-sensing and GABA(B) receptors [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 10, 2024, from https://doi.org/10.69645/RERY7138.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Qing R. Fan has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: G Protein-Coupled Receptors (GPCRs) Signaling in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Qing Fan.
I'm from Colombia University.
The research in my lab involves
the structural studies of class C G-protein coupled receptors.
0:12
GPCRs are divided into different classes
based on the sequence homology of their trans-membrane domains.
Most GPCRs such as rhodopsin and Beta-2 adrenergic receptor belong to class A.
These receptors contain a seven helix trans-membrane domain and can function as monomers.
The ligand binding site of
the class A receptors is located within the trans-membrane domain.
Landmark studies led by Dr. Kodaka's group revealed that agonist binding directly
induces conformational changes among the trans-membrane helices for receptor activation.
Class C GPCRs mediate a number of
key biological phenomena including excitatory and inhibitory neurotransmission,
calcium homeostasis, and taste.
Unlike the class A receptors,
the class GPCRs are characterized by a large extracellular domain.
In addition to the canonical seven helix trans-membrane domain,
this extracellular domain is 500-600 amino
acids long and contains the orthosteric ligand binding site.
Another unique feature of
the class C receptors is that they require dimerization for function.
While metabotropic glutamate receptors and calcium sensing
receptor function as disulfide-linked homodimers,
GABA B receptor and taste receptors are obligatory heterodimers.
Our goal is to use structural methods to probe
the signal transduction mechanisms of class C receptors and GPCR dimers in general.
Specifically, we're focusing on human GABA B receptor and human calcium sensing receptor.
Hide