Generation of cell-surface-targeted fluorescent sensor proteins.

Progress in understanding signal transduction and metabolic pathways is hampered by a shortage of suitable sensors for tracking metabolites, second messengers, and neurotransmitters in living cells. The groups of Prof. Kai Johnsson and Prof. Horst Vogel (ISIC -  Institute of Bioengineering, National Centre of Competence in Research Chemical Biology) introduce a class of rationally designed semisynthetic fluorescent sensor proteins, called Snifits, for measuring metabolite concentrations on the cell surface of mammalian cells. Functional Snifits are assembled on living cells through two selective chemical labeling reactions of a genetically encoded protein scaffold. Their best Snifit displayed fluorescence intensity ratio changes on living cells significantly higher than any previously reported cell-surface-targeted fluorescent sensor protein. This work establishes a generally applicable and rational strategy for the generation of cell-surface-targeted fluorescent sensor proteins for metabolites of interest.

Brun MA et al., J. Am. Chem. Soc., DOI: 10.1021/ja206915m (2011)