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Related Experiment Videos

Structural genomics on membrane proteins: the MePNet approach.

Kenneth Lundstrom1

  • 1BioXtal, Chemin des Croisettes 22, CH-1066 Epalinges, Switzerland. Kenneth.Lundstrom@mepnet.org

Current Opinion in Drug Discovery & Development
|June 26, 2004
PubMed
Summary

Structural genomics efforts are expanding to include membrane proteins, like G protein-coupled receptors (GPCRs), which are crucial drug targets. The Membrane Protein Network (MePNet) is advancing structural biology for these challenging proteins.

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Area of Science:

  • Structural biology
  • Biochemistry
  • Drug discovery

Background:

  • Membrane proteins represent a significant portion (60-70%) of drug targets, yet constitute less than 1% of available crystal structures.
  • The structural determination of membrane proteins is challenging, limiting their study in structural genomics.
  • Existing structural genomics initiatives have primarily focused on soluble proteins.

Purpose of the Study:

  • To address the underrepresentation of membrane proteins in structural databases.
  • To advance the structural determination of G protein-coupled receptors (GPCRs), a pharmaceutically important class of membrane proteins.
  • To establish functional networks for improving success rates in membrane protein structural biology.

Main Methods:

  • Overexpression of full-length GPCRs in bacterial, yeast, and mammalian cell systems.

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  • Purification of expressed GPCRs.
  • Crystallization studies for structural determination.

    • Main Results:

    • The Membrane Protein Network (MePNet) has initiated studies on over 100 full-length GPCRs.
    • Established protocols for overexpression, purification, and crystallization of GPCRs.
    • Demonstrated the feasibility of large-scale structural studies for membrane proteins.

    Conclusions:

    • Technological advancements and collaborative networks are essential for increasing success rates in membrane protein structural biology.
    • MePNet is actively contributing to the structural understanding of GPCRs, enhancing their potential as drug targets.
    • The focus on membrane proteins by initiatives like MePNet is crucial for pharmaceutical research and development.