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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Signaling pathways
- GPCR conformations and dynamics
- Neurotensin receptor NTSR1
- Tools
- Requirements for crystallization
- Conformational thermostabilization
- NTSR1-GW5 mutant with 6 mutations (1)
- NTSR1-GW5 mutant with 6 mutations (2)
- NTSR1-GW5 (1)
- NTSR1-GW5 (2)
- NTSR1-GW5 is in an active-like conformation
- Rhodopsin
- NTSR1/rhodopsin
- Peptide agonist binding
- NTSR1-GW5 & nucleotide exchange catalyzation
- Stabilizing mutations
- Active-like state stabilizing mutations
- More mutants (1)
- Behavior of LF and ELF mutants
- NTSR1-ELF and NTSR1-LF
- Regions important for NTSR1 signaling (1)
- Prerequisites for G protein activation
- F358 determines W321 side chain orientation
- W321-6.48
- Hydrophobic cascade (1)
- L310 causes R167 side chain to re-orient (1)
- L310 causes R167 side chain to re-orient (2)
- More mutants (2)
- Inositolphosphate (IP) production in mutants
- Effect of neurotensin on IP production
- Regions important for NTSR1 signaling (2)
- NTSR1-EL
- Hydrophobic cascade (2)
- Connector (1)
- Connector (2)
- Packing of connector residues
- Dynamics of the G protein coupling interface
- G protein coupling interface
- Agonist-induced constitutive signaling of NTSR1
- Conclusions
- Thank you
- References
Topics Covered
- G protein-coupled receptors
- Neurotensin receptor
- Peptide agonist neurotensin tools for crystallization of membrane proteins
- Conformational thermostabilization
- Crystal structure of NTSR1-GW5
- Binding mode of neurotensin
- Crystal structures of NTSR1-ELF & NTSR1-LF-prerequisites for G protein activation
- Crystal structure of NTSR1-EL
- Constitutive activity
- Molecular dynamics simulations
Links
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Talk Citation
Grisshammer, R. (2019, July 31). Structural and mechanistic insights into the neurotensin receptor [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 5, 2024, from https://doi.org/10.69645/CQZX7842.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Reinhard Grisshammer 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 Reinhard Grisshammer.
I am at the National Cancer Institute,
at the National Institutes of Health in Bethesda, Maryland.
The title of my talk is
structural and mechanistic insights into the neurotensin receptor.
0:20
The outline of my talk is as follows;
I will give a brief introduction into GPCRs,
G protein-coupled receptors and the neurotensin NTSR1.
Then, I will talk about conformational thermostabilization,
which is a technique to make proteins more amenable for crystallization.
Then, I will present four neurotensin receptors structures.
The first one is called NTSR1-GW5,
which has an active-like conformation and
provides insight into the neurotensin peptide binding mode.
Two more structures called NTSR1-ELF and LF
provide insight into the structural prerequisites of G protein activation.
The last structure is of a construct called EL which shows constitutive activity,
where we can learn about the structural features of a constitutively active receptor.
In the end, I will summarize constitutive and
agonist-induced signaling of the neurotensin receptor NTSR1.