Chamma, I. et al. Nat. Commun. http://dx.doi.org/10.1038/ncomms10773 (2016).

Super-resolution microscopy can be used to image cellular structures at nanometer resolution. At such resolution, the use of large tags such as antibodies to label proteins can obscure real structural details, creating a need for better tools for protein labeling. Chamma et al. describe an improved strategy for labeling membrane proteins for super-resolution imaging. They genetically tagged a membrane protein of interest with a short tag that was enzymatically biotinylated. This biotin was then bound by purified fluorescently labeled monomeric streptavidin (mSA). mSA is small tag, and the researchers showed that it does not perturb tagged proteins. The team demonstrated that the labeling strategy worked for μPAINT, STED and dSTORM imaging of several proteins, including synaptic adhesion proteins, and that the method works in two-color imaging applications with a GFP nanobody.