Development of Lanthanide-binding tags (LBTs) for in vivo applications

BIOL 38

Anne M. Reynolds, areynold@mit.edu, Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave. 18-563, Cambridge, MA 02139 and Barbara Imperiali, imper@mit.edu, Department of Chemistry and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139.
Lanthanide-binding tags (LBTs) are small, genetically encodable, and versatile protein fusion partners that selectively bind lanthanide ions with high affinity. Evolved from Ca(II)-binding loops, these 20-amino acid tags feature strategically positioned tryptophan residues that can sensitize Tb(III) luminescence. LBTs thus have the potential for use in varied applications, such as luminescence spectroscopy, luminescence resonance energy transfer, X-ray crystallography and NMR spectroscopy. With the goal of ultimately using LBTs as luminescent probes in vivo, we have incorporated LBTs into interleukin-1ß, a 17-kDa proinflammatory cytokine, using a variety of chemical and molecular biological techniques. We have generated several IL1ß-LBT constructs, by attaching an LBT to either protein terminus or by inserting it into a preexisting protein loop. We have also expanded the scope of LBTs by incorporating sensitizers other than tryptophan, which can sensitize both Tb(III) and Eu(III) luminescence using longer wavelength excitation.