The price of tags in protein localization studies

These continue to be heady times for bacterial cell biology, bothfor experimentalists and formodelers. The ability to follow the dynamics of fluorescently labeled proteins has had a huge impact in understanding the organization of DNA, RNA, and protein complexes in all cells, particularly in bacteria, which do not have many features visible by electron microscopic methods (17). Yet the fluorescent protein tags used for live cell imaging, as well as small epitope tags used for purification and/or immunolocaliza-tion, are a double-edged sword. There have always been suspi-cions that tags could cause localization artifacts, but these suspi-cions usually remain just that, as publishing a paper that claims a previous localization pattern as an artifact requires an extra mea-sure of proof, not just negative data. Swulius and Jensen, in an article in this issue (26), have ob-tained precisely the strong confirmatory evidence needed to refute someprevious published localization patterns. By using cryo-elec