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- Structural and Functional Insights into GPCR Signalling
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1. Structural basis of LSD signaling
- Dr. Daniel Wacker
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3. Structural and mechanistic insights into the neurotensin receptor
- Dr. Reinhard Grisshammer
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5. Biology and structure of arrestin proteins
- Prof. Vsevolod V. Gurevich
-
6. Structure and function of adhesion GPCRs and their ligands
- Prof. Demet Araç
- GPCR signalling in human health and disease
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7. Pre-coupling of receptor oligomers and signaling molecules
- Dr. Sergi Ferré
-
9. G proteins and the biology of depression and antidepressants
- Prof. Mark M. Rasenick
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10. GPCRs and pain
- Prof. Dr. Christoph Stein
-
11. Adhesion GPCRs in nervous system development and disease
- Prof. Tobias Langenhan
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12. G proteins and GPCRs in cancer
- Prof. J. Silvio Gutkind
- Methods to Study GPCRs and Applications of GPCR Engineering
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13. Computational modelling of GPCR signalling dynamics
- Dr. Graham Ladds
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14. Super-resolution imaging of GPCR oligomers: applications and functional roles
- Dr. Aylin Hanyaloglu
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15. Applications of mini G proteins to study G protein-coupled receptors
- Dr. Byron Carpenter
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16. What can we learn from conformational profiling of GPCRs?
- Prof. Terry Hébert
- GPCR Drug Discovery
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17. Drugging conformational states of GPCRs
- Prof. Dr. Peter Kolb
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18. Conserved allosteric sodium in class A GPCRs: GPCR structure and allosteric effects
- Dr. Vsevolod “Seva” Katritch
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19. Conserved allosteric sodium in class A GPCRs: Na+ dynamics in GPCR signaling
- Dr. Vsevolod “Seva” Katritch
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20. Biased signaling at mu opioid receptor splice variants
- Prof. Ying-Xian Pan
Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- GPCRs in human biology & pharmacology
- GPCRs: natural sensors on cell surface
- GPCR structure and function
- Dynamic mechanisms of GPCR action on atomic level
- Human A2a Activation by UK-432097 (R″)
- Activation related changes in Microswitches
- Endogenous allosteric molecules in 1.8 Å structure of human A2AAR
- Allosteric sodium ion in 1.8 Å structure of human δ-Opioid receptor
- Allosteric Na+ site in class A GPCR structures
- Functional conservation of Na+ site in class A GPCR structures
- Structural Conservation of Na+ Pocket in Class A GPCRs
- Conservation of Na+ pocket in the whole Class A GPCRs
- Only 5% of Class A GPCRs lack D2.50
- Collapse of the Na+ pocket in GPCR activation
- Collapse of Na+ pocket upon activation of Opioid receptors: KOR
- Outline (2)
- Early discovery of allosteric Na+ effects on agonist binding in “Opiate” receptors
- Allosteric Na+ effects on agonist binding and signaling have been described for >30 diverse GPCRs
- Binding affinity of Na+ can be measured by its allosteric effect
Topics Covered
- GPCRs structure and function
- GPCRs in human biology and pharmacology
- Conserved Na+ site in class A GPCRs
- Structural modification of Na+ pocket in GPCRs upon activation
- Allosteric Na+ effects on agonist binding in ‘opiate’ receptors
Links
Series:
Categories:
Talk Citation
Katritch, V.“. (2019, December 31). Conserved allosteric sodium in class A GPCRs: GPCR structure and allosteric effects [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved May 1, 2024, from https://hstalks.com/bs/4124/.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Vsevolod “Seva” Katritch has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Conserved allosteric sodium in class A GPCRs: GPCR structure and allosteric effects
Published on December 31, 2019
32 min
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:00
Hello. My name is Seva Katrich and I'm
a computational biologist and a computational chemist from
The Bridge Institute and Michelson Center for
Convergent Bioscience at the University of Southern California in Los Angeles.
So, today, we're going to talk about conserved allosteric sodium ions in class A GPCRs.
0:22
The brief outline of the talk today-
we'll discuss conserved sodium sites from a structural perspective.
We'll discuss early evidence for selective sodium allosteric effects in GPCRs.
We'll describe a theory or hypothesis for
sodium as a key allosteric cofactor in GPCR signaling mechanisms.
I will describe some current studies on
sodium dynamics and potential for sodium site protonation.
We'll also touch a little bit about our attempts for
practical applications from the knowledge about sodium site,
including mutations of sodium pocket and
including design of bitopic ligand targeting sodium pocket,
and then I will give a brief summary.
1:14
A little bit of an introduction of GPCRs in human biology and pharmacology.
As you're well aware,
there are more than 800 G-protein-coupled receptors
and they are omnipresent in our human body.
They're involved in all signaling systems as neurotransmitters.
You can see some familiar names like adrenaline,
dopamine, ligands that activate corresponding G-protein-coupled receptors
and they react to hormones and neuropeptides.
They're involved in the immune system, in embryo development,
and in practically all sensory functions of the human body.
Not surprisingly, more than 30 percent of all drugs in clinics target GPCRs.
There are more than 120 established targets,
and basically, any G-protein-coupled receptor can be a target-
probably olfactory receptors are less targetable.
But, still, all chronic diseases especially,
including in the central nervous system,
so psychiatric or sleep disorders,
drug addiction, in the cardiovascular system,
in the endocrine, in the immune system,
they are targets for neurodegenerative and autoimmune disease and all the way to cancer.
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