Smart “Lanthano” Proteins for Phospholipid Sensing

Metal-ion-mediated interactions between calcium-binding peripheral proteins and membrane phospholipids is a key feature of multiple cell signaling processes. The molecular basis for the interaction involves the displacement of inner-sphere water molecules on calcium ions by phosphate groups of the phospholipids. On the basis of this fundamental mechanism, we have devised a novel “turn-on” optical sensing strategy for anionic phospholipids by using a lanthanide reconstituted protein. The “lanthano” protein turns on selectively in the presence of a crucial signaling phospholipid, phosphatidylserine, by affording a 6 times enhancement in lanthanide luminescence. The “turn-on” sensing strategy was distinctly validated by direct evidence for the water-displacement mechanism via lifetime measurements