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Related Concept Videos

G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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CRISPR01:59

CRISPR

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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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Drug-Receptor Interactions01:29

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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.
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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.
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Related Experiment Video

Updated: Feb 2, 2026

Avidity-based Extracellular Interaction Screening AVEXIS for the Scalable Detection of Low-affinity Extracellular Receptor-Ligand Interactions
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Pooled extracellular receptor-ligand interaction screening using CRISPR activation.

Zheng-Shan Chong1, Shuhei Ohnishi2, Kosuke Yusa2

  • 1Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK.

Genome Biology
|November 28, 2018
PubMed
Summary
This summary is machine-generated.

Identifying cell surface receptors and their ligands is challenging. This study introduces a CRISPR activation method to discover these interactions, successfully identifying myelin-associated inhibitory proteins as ligands for ADGRB1.

Keywords:
CRISPR activationCell signalingCell surface receptorsExtracellular protein interactionsFlow cytometryG-protein-coupled receptorGenome-wide screeningMonoclonal antibodies

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Avidity-based Extracellular Interaction Screening AVEXIS for the Scalable Detection of Low-affinity Extracellular Receptor-Ligand Interactions
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Extracellular Protein Microarray Technology for High Throughput Detection of Low Affinity Receptor-Ligand Interactions
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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genomics

Background:

  • Extracellular interactions involving cell surface receptors are crucial for cellular signaling and adhesion.
  • Identifying specific receptor-ligand pairs remains a significant technical hurdle in biological research.

Purpose of the Study:

  • To develop and validate a genome-wide, cell-based CRISPR activation screening method for identifying receptors of defined ligands.
  • To apply this novel technique to discover ligands for adhesion G-protein-coupled receptors (GPCRs).

Main Methods:

  • Utilized CRISPR activation (CRISPRa) screening in a cell-based system.
  • Employed pooled and individual binding probe strategies to identify receptor-ligand interactions.
  • Applied the method to investigate ligands for adhesion GPCRs.

Main Results:

  • Demonstrated the ability to unambiguously identify receptors for both high-affinity antibodies and low-affinity ligands.
  • Successfully identified Nogo myelin-associated inhibitory proteins as ligands for the adhesion G-protein-coupled receptor B1 (ADGRB1).

Conclusions:

  • The developed CRISPRa-based method provides a powerful tool for large-scale identification of extracellular receptor-ligand pairs.
  • This approach significantly advances the ability to map cell surface receptor-ligand interactions across the genome.