Hundreds Of Cell-surface Proteins Can Be Simultaneously Studied With New Technique (via ScienceDaily)
A new method now enables ETH-Zurich researchers to study hundreds of cell-surface proteins simultaneously. The results obtained could help to develop more accurate diagnostic tests and more specific therapies in the future….
How?
The overview of the cell surface and the proteins present there is possible due to a couple of tricks: “In order to examine the cell surface proteins more specifically, we make use of the fact that they are nearly all glycoproteins”, says Wollscheid. These proteins contain at least one sugar molecule somewhere. The researchers attach a kind of adapter to these sugar molecules, which binds firmly to the sugar residue. In the next step, all the glycoproteins throughout the cell are broken into small fragments using an enzyme, which acts as a pair of molecular scissors. The researchers can then use the matching counterpart to the adaptor to easily pull out any fragments of protein that are attached to the sugar residue, i.e. which come from the cell surface. The researchers thus obtain fragments of the tagged cell surface proteins. Before they can be identified, the sugar residue and the adaptor have to be removed using another enzyme.
The researchers subsequently analyze their collection of protein fragments in the mass spectrometer to obtain information on the composition and mass of the fragments. “With the aid of protein databanks, such as SwissProt, we can identify the corresponding proteins and obtain a list of all the proteins that were present on the cell surface at a particular time”, explains Wollscheid. For some of them, the researchers were surprised to detect the presence of certain proteins on the cell surface, since it was not known previously that they were even there at all. It is also fascinating that so many proteins can be detected in one single experiment….
Why is this useful?
Where previously four to five proteins and their corresponding antibodies were available to characterize a somatic cell or cancer form, but now cells can now be defined via the entire assembly of their cell surface proteins. In order to distinguish between different cell types or cancer forms or stages, one can now look specifically for differences in the quantity and type of the proteins on the cell surface. This allows in the future the selection of cancer specific cell surface proteins for clinical diagnostic and the development of specific sets of antibodies.