The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
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.
Doyle
D A
DA
Laboratory of Molecular Neurobiology and Biophysics and the Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Morais Cabral
J
J
Pfuetzner
R A
RA
Kuo
A
A
Gulbis
J M
JM
Cohen
S L
SL
Chait
B T
BT
MacKinnon
R
R
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D002586:Cesium / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D005583:Fourier Analysis; D006860:Hydrogen Bonding; D008051:Lipid Bilayers; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012413:Rubidium / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D055672:Static Electricity; D013302:Streptomyces / Q000737:chemistry; D019789:Tetraethylammonium / Q000378:metabolism / Q000494:pharmacology; D014867:Water
D001426:Bacterial Proteins; D008051:Lipid Bilayers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; C107790:prokaryotic potassium channel; D014867:Water; D002586:Cesium; D019789:Tetraethylammonium; D012964:Sodium; D012413:Rubidium; D011188:Potassium