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Science 3 April 1998:
Vol. 280. no. 5360, pp. 69 - 77
DOI: 10.1126/science.280.5360.69
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Research Articles

The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity

Declan A. Doyle, João Morais Cabral, Richard A. Pfuetzner, Anling Kuo, Jacqueline M. Gulbis, Steven L. Cohen, Brian T. Chait, Roderick MacKinnon *

The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains two K+ ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter. The architecture of the pore establishes the physical principles underlying selective K+ conduction.

D. A. Doyle, R. A. Pfuetzner, A. Kuo, and R. MacKinnon are in the Laboratory of Molecular Neurobiology and Biophysics and the Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. J. M. Cabral and J. M. Gulbis are in the Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. S. L. Cohen and B. T. Chait are in the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
*   To whom correspondence should be addressed. E-mail: mackinn{at}rockvax.rockefeller.edu

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