Surprising shape of key cellular pore unveiled. (Paddle Power).Underlying every thought and bodily motion are nerve and muscle cells sending or receiving electrical signals. Driving this activity are voltage-gated ion channels--pores that quickly open or dose to various ions depending on the electrical properties of the cell's membrane. A research team has now obtained the first atomic-scale portrait of one of these crucial gatekeepers, a voltage-dependent potassium channel In cell biology, potassium channels are the most common type of ion channel. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cells and control cell function. . "It looks very different than any of us expected," says team leader Roderick MacKinnon Roderick MacKinnon (born 19 February 1956 in Burlington, Massachusetts) is a professor of Molecular Neurobiology and Biophysics at Rockefeller University who won the Nobel Prize in Chemistry together with Peter Agre in 2003 for his work on the structure and operation of ion , a Howard Hughes Medical Institute Howard Hughes Medical Institute, (HHMI), nonprofit medical research organization founded in 1953 by Howard Hughes and largly funded from proceeds of the 1984–85 sale of Hughes Aircraft. Headquartered in Chevy Chase, Md. (HHMI HHMI Howard Hughes Medical Institute HHMI Hispanic Healthy Marriage Initiative ) investigator at Rockefeller University in New York New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of Over the past 6 years, in work that some scientists predict will earn a Nobel prize Nobel Prize, award given for outstanding achievement in physics, chemistry, physiology or medicine, peace, or literature. The awards were established by the will of Alfred Nobel, who left a fund to provide annual prizes in the five areas listed above. , MacKinnon's team isolated the proteins that make up various kinds of ion channels, coaxed them into forming stable crystals, and beamed X rays through the crystals to locate the positions of atoms within the pores. From such data, the researchers uncovered often-unexpected structures for channels that regulate the flow of potassium, sodium, calcium, and other ions (SN: 3/9/02, p. 152). However, voltage-dependent ion channels resisted the team's attempts at crystallization Crystallization The formation of a solid from a solution, melt, vapor, or a different solid phase. Crystallization from solution is an important industrial operation because of the large number of materials marketed as crystalline particles. . MacKinnon and his colleagues finally circumvented that obstacle by binding an antibody to each of the four subunits that make up a voltage-dependent potassium channel. This stabilized the structure enough to form crystals that the investigators could analyze. Most scientists had thought that the voltage-sensing regions of the pore would be hidden within the ion channel, but instead they jut out as hinged projections that MacKinnon calls "paddles" In hindsight, he adds, it's clear that the free-moving nature of these four, positively charged paddles accounts, at least in part, for the difficulties in crystallizing the pores. Taking into account the new structure and several follow-up experiments, all described in the May 1 Nature, MacKinnon's team has offered a proposal for how voltage-gated ion channels work. When the inner portion of a cell membrane Cell membrane The membrane that surrounds the cytoplasm of a cell; it is also called the plasma membrane or, in a more general sense, a unit membrane. This is a very thin, semifluid, sheetlike structure made of four continuous monolayers of molecules. has a negative charge, the paddles of the pore are attracted to it and extend horizontally along that inner membrane, keeping the channel closed. If the outer half of the cell membrane becomes negatively charged, however, the paddles assume a vertical position by swinging on their hinges toward that charge. "That moving up pulls the pore open, suggests MacKinnon. "The structure is a complete surprise to the field," says David Clapham, an HHMI investigator at Children's Hospital in Boston. Most ion-channel researchers had never envisioned such large movements by the voltage-sensing parts of the pores. "I am awed by the high quality of the work and the courage of the interpretation," says Clapham. The potassium channel that MacKinnon's team probed actually comes from a bacterium, so scientists don't yet know whether its structure reflects a general shape for all voltage-gated ion channels, notes Clapham, who studies a voltage-sensitive sodium channel. Because the amino acid amino acid (əmē`nō), any one of a class of simple organic compounds containing carbon, hydrogen, oxygen, nitrogen, and in certain cases sulfur. These compounds are the building blocks of proteins. makeup of the bacterial potassium channel is similar to that of other voltage-gated channels, especially in the paddle regions, it's likely that all such channels operate in the same way, predicts MacKinnon. The discovery that the voltage sensors of the ion channel are more exposed than scientists had expected may interest those looking for Looking for In the context of general equities, this describing a buy interest in which a dealer is asked to offer stock, often involving a capital commitment. Antithesis of in touch with. drugs that influence nerve or muscle activity. "I'm thinking now very differently about potential targets for drugs," says MacKinnon. "I think these paddles are very promising targets." |
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