Ion channel opens like bud
First insight into the opening structure of electrical signal transmission in nerve cellsRead out
Ion channels are the key to every nerve and muscle activity. Now researchers have first decrypted the structure of such a channel in the open state. They discovered, among other things, that the opening of the five subunits equals the movement of a rising cospec. The study, now published in Nature, provides the first detailed insight into a fundamental mechanism of electrical signal transmission.
Ion channels are the electrical switches of our cells. They allow the controlled flow of charged ions through the cell membrane. This process forms the basis for all electrically controlled processes from nerve stimulation to muscle movement. To enable these complex processes, the ion flux must be controlled. Therefore, ion channels can be controlled opened and closed by signals. Different neurotransmitter receptors in nerve cell synapses are part of a protein family of ligand-dependent ion channels.
In the absence of the neurotransmitter, these channels are closed, blocking the passage of ions through the membrane. However, when certain neurotransmitters are released, they bind to the receptor, whereupon the channel opens and allows certain ions to flow through the membrane. The protein family includes, among others, acetylcholine and GABA receptors whose malfunction leads to severe nerve and muscle diseases and which are important targets for
Closed state was not enough
"To understand how these neurotransmitter receptors work, we need to know their three-dimensional structures in a closed state as well as in an open state, " explains Professor Raimund Dutzler. Eight months ago, he and his research group presented the first detailed structure of a closed receptor at the Biochemical Institute of the University of Zurich. display
Although this structure showed the blueprint of this protein family, it was impossible to conclude by a structure on the mechanism of the opening and the selective ion flux. The group has now succeeded in elucidating the structure of a related ion channel in the open state using X-ray crystallography. As in the previous study, scientists used close bacterial relatives of neurotransmitter receptors.
"The two structures are derived from different channels, but the proteins are similar enough to understand the structural change in the opening of the pore, " explains Dutzler. The structures and functional mechanisms within a protein family are so conserved that it is possible to deduce the structures of these bacterial proteins as well as their human relatives.
Opening like bud
"The result of the investigation is unexpected, " says Dutzler. "It shows an opening mechanism that contradicts the traditional picture of this process." Upon opening, the parts of the protein that make up the channel move as a rigid entity. Since the protein consists of five equal subunits, which perform the same movements, the channel opens similar to an inflating bud. The movements are much larger than expected However, the structure is consistent with the results of decades of experimental research.
According to Dozer, the two structures allow insight into a mechanism that must now be confirmed by new experiments. He is convinced that the insights gained will find their way into the textbooks and will be of great importance for the development of new drugs for neurotransmitter receptors.
(University of Zurich, 06.11.2008 - NPO)