Proteome chips – a tantalizing new flavor

In a landmark study, investigators from Yale and North Carolina State Universities report the simultaneous analysis of practically every protein encoded by the yeast genome [Zhu, H. et al. (2001) Science Express Reports 10.1126/science.1062191]. The group, led by Michael Snyder, made ‘proteome chips’ comprising microarrays of 5800 different proteins (93.5% of all yeast ORFs) and tested their ability to bind to various biomolecules. Using calmodulin as a probe, six previously known, and thirty-three novel, binding proteins were identified. However, four other calmodulin-binding proteins were not detected as they were present at very low levels on the chip. Interactions with various lipids were also tested and confirmed by independent techniques. By developing a high-throughput approach, the group was able to overcome the formidable obstacle of cloning, expressing and purifying a very large number of proteins. Similar methods should allow the preparation of arrays using the proteome of any organism whose genome has been sequenced. Some fine-tuning is necessary to ensure representation of specifically modified proteins and those that are poorly or improperly expressed. However, proteome chips are set to become a major new tool in biomedical research as they permit the screening of a comprehensive and defined set of proteins for a variety of activities, including posttranslational modifications and interactions with other proteins and pharmaceutical compounds. S.L.