Jerusalem -- The structure of the membraneprotein NhaA has been revealed by researchers at the Hebrew Universityof Jerusalem and the Max Planck Institute of Germany.
Membrane protein research is at the forefront of modernbiological study, with great potential consequences for development ofnew medicinal treatments and genetic engineering of plants.
The research on NhaA has been carried out by Etana Padan, theAdelina and Massimo DellaPergola Professor of Life Sciences, with Dr.Rimon Avraham, both of the Silberman Institute of Life Sciences at theHebrew University, and Prof. Hartmut Michel, Nobel prize winner forchemistry in 1988, of the Max Planck for biophysics in Frankfurt,Germany. Their work, described in a recent edition of the journalNature, was supported by a grant from the German-Israel BinationalScience Foundation;
Proteins such as NhaA are found in the membranes of everyliving cell, from bacteria and up to humans. Until now, the structureof fewer than 50 cell membrane proteins have been discovered, asopposed to 30,000 soluble proteins.
"The location of the proteins in the cell membranes presentstremendous difficulties in research," said Prof. Padan. "Unlike themajority of those proteins which are soluble in water, the membraneproteins are soluble only in fats or in the presence of detergents."
The cell membrane is the crossroads of busy, two-way "traffic"through which materials and impulses travel into and out of the cell.The fatty cell membrane is impenetrable to most of these materials andsignals; and it is therefore the proteins within the membranes that areresponsible for the communication between the cell and its environment.Indeed, more than 60 percent of the medicines in use today are directedat the cell membrane proteins. Since the cell membrane proteins areexposed, in part, to areas extending outside the cells, the medicinesare able to reach them without entering the cell itself.
In Prof. Padan's laboratory, the researchers succeeded inisolating the gene that encodes NhaA in bacteria and in producing alarge quantity of the protein in its active state. This achievementpaved the way for determining the structure of the protein, providingan essential insight into its mechanism of activity and regulation.NhaA protects the volume of the cell and its internal, normative statein terms of its salinity and acidity.
The deciphering of the NhaA protein's structure was doneutilizing three-dimensional crystals of the protein which diffractx-rays. The work of analyzing the diffraction was done using thepowerful electron accelerators in Grenoble, France, and Zurich,Switzerland.
"In this way we were able to reveal the wonderful architectureof the membrane protein, which was unknown before," said Prof. Padan."In the center of the protein we found a wide funnel which extends intothe cell. The funnel narrows and ends at the point at which it bindswith the sodium or the hydrogen deep within the cell membrane. Nearthat point two chains of the protein unite into a unique structure."
The researchers believe that this unique structure is thebasis for the activity of the protein. The protein operates as a kindof pump, utilizing energy which it receives from processes taking placewithin the cell. The protein structure thus acts as a kind of molecularmotor. This "motor" is connected to the area found at the mouth of thefunnel that apparently conveys signals to "modulate" the motoraccording to the acidity within the cell. The result is that theprotein's activity is controlled in accordance with the needs of thecell in relation to its acidic and basic levels.
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