Technology reveals 'lock and key' proteins behind diseases

 
A University of Toronto press release [here] announces a paper that's just been published in Molecular Cell [Paumi et al. 2007].

Paumi, C.M., Menendez, J., Arnoldo, A., Engels, E., Iyer, K.R., Thaminy, S., Georgiev, O., Barral, Y., Michaelis, S., and Stagljar, I. (2007) Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid Analysis. Molecular Cell 26:15-25.

One of the lead authors is my friend Igor Stagljar (that's him in the picture). The study is a collaboration between him and Susan Michaelis' group at Johns Hopkins in Baltimore MD (USA). It's a pretty decent press release without too much hype. I just wish there was more emphasis on basic biochemistry and less on possible applications in medicine. The paper describes a new technique called "Integrated Split-Ubiquitin Yeast Two-Hybrid Analysis" or iMYTH—a variant of MYTH technology. The paper has nothing to do with medicine.

The idea is to identify proteins that interact with membrane bound proteins. There are many membrane receptors that have been identified in the human genome on the basis of their similarity to known receptors. Their functions are unknown and one way to discover what they do is to detect other, hopefully known, proteins that bind to the receptors. The MYTH technology has been used to identify these interactions since it was first developed by Igor almost ten years ago. The modification in this paper is to integrate the "bait" construct into the yeast genome thus improving the sensitivity of detection (see Figure 1).

This is a proof of principle paper using a yeast ABC transporter that's being characterized by the Michaelis lab. Paumi et al. were able to identify six proteins that interact with the transporter, including Tus1P, a well-characterized guanine nucleotide exchange factor (GEF).

The exciting thing about this technique is that Igor has just introduced it into our Advanced Biochemistry Lab for undergraduates [BCH471Y]. The students are completing the final discussion day today. They identified a number of different proteins from a human brain library that interact with a human membrane receptor. One of them was a protein that had escaped detection when the experiments were first done in the Stadljar lab.