Recently, a research team from Korea and the United States reported a new method for manipulating the folding of membrane proteins in a membrane environment. They called the new tool a magnetic tweezer.
Proteins http://www.cusabio.com/ are big biomolecules that contain hundreds to thousands of atoms. The atoms adopt a unique three dimensional structure, placing chemical groups in just the right place. Thus proteins can catalyze reactions or build cellular structures.
Since seeing the first structures of protein in 1950s, molecular biologists have been confused about how all the atoms manage to find the right location, that is the so-called folding problem. Furthermore, folding has important medical implications for most genetic defects cause protein misfolding.
About a third of all proteins float around in the cell membrane where they ensure the right chemicals get in the cell in the right amounts. Membrane proteins also provide key information links between the cell and its environment. In fact, most drugs target membrane proteins. However, the folding of membrane proteins has been particularly difficult to study and has rarely been studied in its natural environments. So the folding process of most proteins still remains unknown.
In order to understand the process better, the researchers first attached long DNA handles to the ends of the protein. One handle is attached to a glass surface and the other to a magnetic bead. Using a magnet, they can essentially grab the protein and pull on it, inducing it to unfold. By playing with the bead attached to the protein, they can force the protein to unfold or allow it to refold, and watch all this happening by 3D-tracking of the magnetic bead. With this novel strategy, they were able to quantitatively map the folding energy landscape, the folding kinetic rate, and folding intermediates of a membrane protein in a membrane environment for the first time.
Surprisingly, all the atoms of the protein jump into the correct structure together. The researchers expected that the protein structure would come together in a more piecemeal fashion, with different parts of the structure forming separately, but that was not the case.
It is possible that nature evolved such a smooth, highly cooperative folding process to prevent partially folded forms that could get into trouble in the crowded cell membrane. On the other hand, the cooperative folding seen here might not apply to other membrane proteins. More proteins need to be studied.
The single molecule mechanical manipulation technique could enable detailed folding studies of many other membrane proteins. Previously, the major barrier to membrane protein study is that the proteins tend to stick together and get tangled up.
Now, scientists can observe the folding and unfolding of a single membrane protein using magnetic tweezers. The protein cords are held apart from other cords with the tweezer technique. So the proteins http://www.cusabio.com/catalog-13-1.html cannot get tangled up anymore.
The researchers hope that the novel approach will open a door to an important part of the protein study to scrutiny, including the proteins that misfold in disease states.
