Catching interacting proteins red-handed
Nature Methods
A new chemical modification strategy enables researchers to directly link almost any protein to its functional accomplices within the cell. This simplifies the study of protein interaction like never before, according to a report in the April issue of Nature Methods.
Like participants in an elaborate heist, proteins seldom work alone. Their success depends on tightly coordinated teamwork with other proteins, with which they associate to form larger, multi-member complexes. Understanding these associations is vital to understanding protein function, but many occur only transiently, and may be missed or even disrupted during an experiment.
Cross-linking, wherein two associated proteins are linked via a chemical reaction, offers one solution for 'trapping' even brief protein-protein interactions. One common cross-linking strategy relies on the use of chemicals such as paraformaldehyde, although these can hamper further analysis. Alternatively, one can use specially engineered proteins containing cross-linkable chemical groups, but these require considerable effort to generate, and enable the study of only a single protein at a time.
Christoph Thiele and colleagues present an exciting new alternative: modified amino acids that are readily taken up by cultured cells and, without any further tinkering, incorporated into newly synthesized proteins. When exposed to ultraviolet light, these modified amino acids undergo a rapid alteration that enables them to cross-link with other nearby proteins. These photoreactive residues are neither toxic to cells, nor do they interfere with normal protein function. Thiele's team demonstrates that their cross-linking approach can confirm previously identified protein interactions, as well as revealing completely novel interactions.
This method can be applied to any protein expressed by cells cultured in the presence of these compounds, potentially simplifying the dissection of even the most elaborate multi-protein complexes.
CONTACT
Christoph Thiele (Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany)
Tel: +49 351 210 2622, E-mail: thiele@mpi-cbg.de
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