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Higher order structure and function of biomembranes

Final Report Summary - BIOMEMOS (Higher order structure and function of biomembranes)

Biomembrane form important barriers between cells and the surrounding environment and separate also compartments and organelles inside the cell. Membrane proteins integrated into the lipid bilayer membrane functionalize the biomembranes for specific structural and enzymatic purposes and undertake the key processes of transport and signaling across the membrane that allow a cell to sense, interact and exchange with the environment. Typically, the cell membrane also defines an electrical potential with the inside being negatively charged at a voltage of about -60 mV. The BIOMEMOS project has addressed the structure and function of such cell membranes, with a particular focus on the regulation and interaction of P-type ATPases and how they interact with the membrane and other proteins. Members of this family maintain steep electrochemical gradients for ions like H+, Na+, K+ and Ca2+, and also a tightly controlled level of vital, but also potentially toxic metal ions like Cu+. Hence, P-type ATPases can be considered as energy transformers that exchange chemical energy in the form of ATP into electrical energy in the form of ion gradients that also form the membrane potential, and they consume a major share of the energy produced in a cell, approaching 70% in certain areas of the brain.
The BIOMEMOS project has revealed a number of important details of the structure, function and mechanism of P-type ATPases, and the findings have been disseminated through numerous channels ranging from the most prestigious scientific journals to industry collaborations, innovation projects, and broadcasts in public media. As one example new insight into the regulation of the highly active calcium pump in muscle tissue by membrane lipids and how it is slowed down by a small protein called sarcolipin, which is also implicated in the regulation of the body temperature. Another good example is a series of studies of the sodium-potassium pump on how it pumps Na+ ions out of the cell and is affected by mutations associated with neurological diseases and Conn's disease causing hypertension. Another important aspect of BIOMEMOS has been in methods development, and a number of new methods and approaches in membrane research of general interest to a large community has been developed aiming also for new future research activities and biotechnology.