BioDrugs

, Volume 17, Issue 6, pp 413–424 | Cite as

Yeast Genetic Methods for the Detection of Membrane Protein Interactions

Potential Use in Drug Discovery
Technology Review

Abstract

Due to the pivotal role of membrane proteins in many cellular processes, their direct link to human disease and their often extracellular accessibility towards drugs, an understanding of membrane protein function is desirable. However, the hydrophobic nature of membrane proteins often results in insoluble proteins which makes protein isolation difficult and therefore hinders the determination of protein complex composition and protein function. Recently, several yeast genetic techniques have made the characterisation of interactions among membrane proteins more feasible. Techniques such as the guanine-nucleotide binding protein fusion assay, the reverse Ras recruitment system and the split-ubiquitin system have been fruitful in monitoring known protein interactions and uncovering novel interactions. Since many disease states have altered membrane protein function, one can use these systems to recreate interactions involving disease causing membrane proteins. Once established, screens for small molecules, peptides and/or single chain antibodies which disrupt such interactions can provide insight into the biology of the interaction and thus help guide therapeutical research. In this review, we speculate on the feasibility of using inhibitors of protein interactions as drugs and the adaptation of these techniques to select for inhibitors of defined protein interactions.

Notes

Acknowledgements

We would like to thank Antonio Bedalov for his helpful discussions and critical reading of the manuscript, and Ulrich Hübscher for his support. The I.S. group is supported by Zürcher Krebsliga, Gebert-Rüf Foundation, EMDO Foundation, Novartis Foundation, Olga Mayenfisch Foundation, Sassella Foundation, Fonds für medizinische Forschung, Kommission für Technische Inovation (KTI, Nr. 5343.2 SUS) and the Swiss National Science Foundation (31-58798.99 and 3100A0-100256/1).

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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Michael Fetchko
    • 1
  • Daniel Auerbach
    • 2
  • Igor Stagljar
    • 1
  1. 1.Institute of Veterinary Biochemistry and Molecular BiologyUniversity of Zurich-IrchelZurichSwitzerland
  2. 2.Dualsystems Biotech Inc.ZurichSwitzerland

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