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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
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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...
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A Receptor for All Occasions.

Darrell J Irvine1

  • 1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; Department of Materials Science & Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; The Ragon Institute of MGH, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, Massachusetts 02139, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

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Summary
This summary is machine-generated.

Scientists engineered synthetic Notch receptors to control cell signaling. This breakthrough allows independent management of cellular inputs and outputs in various cell types.

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Area of Science:

  • Cell biology
  • Synthetic biology
  • Biotechnology

Background:

  • Cell surface receptors mediate communication between cells and their environment.
  • Engineering receptors with controllable inputs and outputs independent of natural cellular pathways remains a significant challenge.

Purpose of the Study:

  • To develop a novel system for engineering cell surface receptors.
  • To achieve independent control over both the inputs and outputs of engineered receptors.

Main Methods:

  • Utilized synthetic Notch receptors as a base for the engineered system.
  • Demonstrated the system's functionality in diverse cell types.

Main Results:

  • Successfully created a system enabling independent control of receptor inputs and outputs.
  • The engineered receptors function orthogonally to endogenous signaling pathways.

Conclusions:

  • The developed synthetic Notch receptor system offers a powerful tool for precise control of cellular functions.
  • This technology has broad implications for cell-based therapies and synthetic biology applications.