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Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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Mitogens and the Cell Cycle02:38

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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GPCR Desensitization01:12

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Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
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Structural basis for EGFR ligand sequestration by Argos.

Daryl E Klein1, Steven E Stayrook, Fumin Shi

  • 1Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.

Nature
|May 27, 2008
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Summary

Argos, a Drosophila protein, binds epidermal growth factor (EGF) ligands to inhibit epidermal growth factor receptor (EGFR) signaling. Its unique clamp-like structure, unrelated to EGFR, offers potential for designing anti-cancer therapeutics.

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Last Updated: Jun 11, 2026

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Area of Science:

  • Structural biology
  • Molecular and cell biology
  • Biochemistry

Background:

  • Epidermal growth factor receptor (EGFR) signaling is crucial for development but implicated in cancer.
  • Argos, a Drosophila protein, inhibits EGFR signaling by binding its ligands.
  • Understanding Argos's structure is key to developing anti-cancer agents.

Purpose of the Study:

  • To determine the crystal structure of Argos bound to an EGFR ligand.
  • To elucidate the molecular mechanism of Argos-mediated EGFR ligand sequestration.
  • To explore potential therapeutic applications of Argos and its structural homologues.

Main Methods:

  • X-ray crystallography at 1.6-A resolution.
  • Structural analysis and comparison with known protein families.
  • Bioinformatics to identify potential mammalian homologues.

Main Results:

  • The crystal structure reveals Argos has a three-domain, clamp-like fold, not an EGF-like domain.
  • Argos binds EGF ligands via a bipartite surface, mimicking EGFR's function.
  • Argos domains share structural similarities with TGF-beta receptors and uPA receptor.

Conclusions:

  • Argos utilizes a novel structural mechanism to sequester EGFR ligands.
  • Mammalian Argos homologues may exist and warrant further investigation.
  • The structure provides a blueprint for designing artificial EGF-sequestering anti-cancer drugs.