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Related Experiment Videos

Structural genomics on membrane proteins: mini review.

K Lundstrom1

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

Combinatorial Chemistry & High Throughput Screening
|August 24, 2004
PubMed
Summary

Structural genomics has focused on soluble proteins, but membrane proteins like GPCRs are crucial drug targets. Developing new technologies for membrane protein structure determination is essential for advancing drug discovery.

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Area of Science:

  • Structural biology
  • Membrane protein research
  • Drug discovery

Background:

  • Structural genomics primarily targets soluble proteins due to easier handling.
  • Membrane proteins, crucial drug targets (60-70%), are underrepresented (<1%) in structural databases.
  • G protein-coupled receptors (GPCRs) are a key class of membrane proteins with pharmaceutical importance.

Purpose of the Study:

  • To address the challenge of determining membrane protein structures.
  • To advance structural genomics for pharmaceutically relevant membrane proteins, specifically GPCRs.
  • To develop and evaluate efficient methodologies for membrane protein structural elucidation.

Main Methods:

  • Employed parallel studies and evaluated various expression systems for a large number of targets.

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  • Established high-throughput screening methods for solubilization and refolding using diverse detergents and additives.
  • Utilized three overexpression systems within the Membrane Protein Network (MePNet) program for 101 GPCRs.

    • Main Results:

    • Generated substantial quantities of recombinant GPCRs suitable for structural biology.
    • Demonstrated the feasibility of large-scale structural genomics approaches for membrane proteins.
    • Laid the groundwork for high-resolution structure determination of pharmaceutically important GPCRs.

    Conclusions:

    • Technology development is key to overcoming challenges in membrane protein structural biology.
    • Parallel, high-throughput approaches are efficient for studying numerous membrane protein targets.
    • Initiatives like MePNet are crucial for advancing the structural understanding of GPCRs for drug discovery.