researchers have created specially engineered mammalian cells to provide a new “chemical handle” which will enable researchers to label proteins of interest
more efficiently, without disrupting the normal function of the proteins
themselves or the cells in which they are found.
Protein labeling is used by researchers in a variety of fields to help them
understand how these important molecules affect the normal functioning of
cells. Currently, proteins are labeled for study simply by fusing them to other
fluorescent proteins, which allows researchers to use microscopy to track their
movements through a cell. This approach has several drawbacks, however, not
least being that the fluorescent proteins are often large enough to affect the
function of the protein of interest.
Alex Deiters, PhD, associate professor of chemistry, along with colleague Jason
Chin, PhD, of the Laboratory of Molecular Biology at the Medical Research
Council in Cambridge, U.K., have developed a way to attach a fluorophore—a
fluorescent molecule about 20 times smaller than the fluorescent proteins
currently in use—to a protein that is expressed in a mammalian cell.
Deiters and Chin developed a special 21st amino acid that they added to
cells that were specially engineered to incorporate this amino acid into the
protein they wanted to study (there are normally only 20 amino acids). This
21st amino acid has a “chemical handle” that only reacts with a specifically
designed fluorophore, but not any cellular components. According to Deiters, “The reaction between the modified protein and the fluorophore is extremely
fast, high yielding, and generates a stable link between both reaction
partners. This novel methodology enables future cell biological studies that were
previously not possible.”
The research appears in Nature Chemistry.
“We found that our approach gave us a higher yield of labeled proteins and
that the binding reaction was 50 times faster than with current methods,”
Deiters says. “Additionally, it took less reagent to complete the reaction, so
overall we have a faster, more efficient method for protein labeling, and less
chance of interfering with the normal function of the proteins and cells being