Risco, C., et al. Structure 20, 759–766 (2012).

A genetically encoded tag for protein identification in transmission electron microscopy would be useful for studying cellular ultrastructure. Some such approaches have been previously reported, but tags that are robust, nonperturbative and enable high-resolution imaging are still needed. Risco et al. built on previous work in vitro and in bacteria to show that the 61–amino acid metal-binding protein metallothionein can serve as such a tag in mammalian cells. They incubated cells expressing a tagged protein with gold salts, which yielded an approximately 1-nanometer gold cluster around each tag. The authors demonstrated that gold, in amounts sufficient for labeling, can enter BHK-21 cells without obvious toxicity and that endogenous cellular metallothionein does not give a detectable signal. They applied the approach to detect rubella virus particles at multiple locations in the cell.