BALTIMORE, Md. Johns Hopkins University researchers here have disclosed a single-molecule switch which was engineered from a strand of a living proteinan enzyme.
According to a Johns Hopkins professor,
Marc Ostermeier the university's patented two-stage switch improves on previous single-stage switches by separating sensitivity from signal-to-noisequantities ordinarily
inversely related (as trade-offs). He presented his work recently [March 27] at the annual meeting of the American Chemical Society in New Orleans.
"We take two proteins with different functions and fuse them in such as way as to form a switch," said Ostermeier who was assisted in his work by doctoral student Gurkan Guntas.
The advantage of fusing two disparate proteins, according to
Ostermeier, is that the protein that recognizes what is to detected doesn't have to provide the signal to the outside world. Instead, it is fused with a protein that produces a very easily detectable signal.
"With our technique you are free to choose a signal transducing
protein that will give you the best signal," said Ostermeier.
In biological parlance, Ostermeier is doing "domain insertion" by splicing together protein sequences with different functions. Ostermeier's sensing proteins exhibit allosteric changes in shape that turn on a molecular switch in the second signaling protein.
Such molecular switches could be applied as super-sensitive sensors that detect even a single molecule of a biological warfare agent, for example.
Medically, molecular switches have even wider-scale potential, from early detection of hard-to-diagnosis maladies, to "lethal drug" delivery only to cancerous cells.
Ostermeier's laboratory studies how to link molecular-level signals such as ligand binding, protein-protein interactions or pH changes, to switches signaling macro-level alerts, such as fluorescing.