Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Types of Receptors: Cell Surface Receptors01:28

Types of Receptors: Cell Surface Receptors

22.1K
Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are...
22.1K
The Two-State Receptor Model01:29

The Two-State Receptor Model

2.6K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
2.6K
Drug-Receptor Interactions01:29

Drug-Receptor Interactions

6.4K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
6.4K
Internal Receptors01:31

Internal Receptors

71.9K
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
71.9K
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

6.7K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
6.7K
Types of Receptors: Internal Receptors01:07

Types of Receptors: Internal Receptors

27.5K
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
27.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

In Science Journals.

Science (New York, N.Y.)Β·2026
Same author

Designer binders.

Science signalingΒ·2026
Same author

Cholinergic signals and antibodies.

Science signalingΒ·2026
Same author

Editorial expression of concern.

Science signalingΒ·2026
Same author

Editorial retraction.

Science signalingΒ·2026
Same author

SIRT2 versus Lck.

Science signalingΒ·2026
Same journal

ZNRF3 and RNF43 are active monomeric E3 ubiquitin ligases that self-associate.

Science signalingΒ·2026
Same journal

Allosteric ligands with distinct properties uncover tissue-specific physiological regulation mediated by free fatty acid receptor 2.

Science signalingΒ·2026
Same journal

Diacylglycerol kinase ΞΆ in B lymphocytes supports CD40-mediated immune synapse formation, mTORC1 signaling, and plasma cell fate.

Science signalingΒ·2026
Same journal

The APC/C adaptor Cdh1 stabilizes STING to potentiate innate immune activation in renal cell carcinoma.

Science signalingΒ·2026
Same journal

Fattening mother's milk with oxytocin.

Science signalingΒ·2026
Same journal

Virion display reveals MD-1 as an endogenous agonist for the orphan receptor GPRC5B.

Science signalingΒ·2026
See all related articles

Related Experiment Video

Updated: Oct 13, 2025

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
10:59

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

3.4K

Interfacing with a receptor.

John F Foley1

  • 1Science Signaling, AAAS, Washington, DC 20005, USA.

Science Signaling
|November 16, 2021
PubMed
Summary
This summary is machine-generated.

Distinct structural interactions enable a single G protein-coupled receptor (GPCR) to engage with two distinct G proteins, influencing cellular signaling pathways.

More Related Videos

High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy
15:13

High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy

Published on: July 25, 2014

11.5K
A BW Reporter System for Studying Receptor-Ligand Interactions
06:05

A BW Reporter System for Studying Receptor-Ligand Interactions

Published on: January 7, 2019

7.8K

Related Experiment Videos

Last Updated: Oct 13, 2025

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
10:59

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

3.4K
High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy
15:13

High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy

Published on: July 25, 2014

11.5K
A BW Reporter System for Studying Receptor-Ligand Interactions
06:05

A BW Reporter System for Studying Receptor-Ligand Interactions

Published on: January 7, 2019

7.8K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • G protein-coupled receptors (GPCRs) are crucial cell surface receptors involved in numerous physiological processes.
  • GPCRs signal by coupling to intracellular heterotrimeric G proteins, initiating diverse downstream effects.
  • Understanding GPCR-G protein interactions is key to deciphering cellular communication and developing targeted therapeutics.

Purpose of the Study:

  • To elucidate the specific structural mechanisms governing the interaction of a single GPCR with multiple G protein subtypes.
  • To investigate how distinct structural interfaces dictate differential G protein coupling.
  • To provide a molecular basis for understanding GPCR signaling promiscuity.

Main Methods:

  • Utilized X-ray crystallography to determine the high-resolution structures of the GPCR in complex with two different G proteins.
  • Employed site-directed mutagenesis to identify key amino acid residues involved in the distinct interactions.
  • Performed functional assays to confirm the impact of structural changes on G protein coupling and downstream signaling.

Main Results:

  • Revealed unique structural footprints at the interface between the GPCR and each G protein subtype.
  • Identified specific receptor residues that mediate differential binding affinities and orientations for the two G proteins.
  • Demonstrated that subtle structural variations dictate the functional outcome of GPCR activation.

Conclusions:

  • The study demonstrates that a single GPCR can couple to distinct G proteins through specific, yet conformationally adaptable, structural interactions.
  • These findings highlight a novel mechanism of signaling regulation at the GPCR-G protein interface.
  • This work provides critical insights into GPCR signal diversity and potential therapeutic targeting strategies.