A molecular blueprint for the pore-forming structure of voltage-gated calcium channels.
A protein that imitates the sequence of a highly conserved segment predicted to line the pore of dihydropyridine-sensitive L-type calcium channels was designed and synthesized. Single-channel conductance properties were studied in planar lipid bilayers. The synthetic protein emulates the ionic conductance, ionic selectivity, and pharmacological properties of the authentic calcium channel, including the stereospecific action of agonist and antagonist enantiomers of the dihydropyridine BayK 8644. The identified sequence is identical in L-type calcium channels from skeletal muscle and isoforms of cardiac muscle, brain, and aorta. It is plausible that this structural motif represents the molecular blueprint for the pore-forming structure of voltage-gated calcium channels.
Grove
A
A
Department of Biology, University of California San Diego, La Jolla 92093-0319.
Tomich
J M
JM
Montal
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D003198:Computer Simulation; D004553:Electric Conductivity; D008051:Lipid Bilayers; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000138:chemical synthesis / Q000648:ultrastructure
D015220:Calcium Channels; D008051:Lipid Bilayers; D011506:Proteins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester