Structure of the sodium channel pore revealed by serial cysteine mutagenesis.
The pores of voltage-gated cation channels are formed by four intramembrane segments that impart selectivity and conductance. Remarkably little is known about the higher order structure of these critical pore-lining or P segments. Serial cysteine mutagenesis reveals a pattern of side-chain accessibility that contradicts currently favored structural models based on alpha-helices or beta-strands. Like the active sites of many enzymes of known structure, the sodium channel pore consists of irregular loop regions.
Pérez-García
M T
MT
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chiamvimonvat
N
N
Marban
E
E
Tomaselli
G F
GF
D000595:Amino Acid Sequence; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D017433:Protein Structure, Secondary; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry* / Q000187:drug effects; D013329:Structure-Activity Relationship; D013779:Tetrodotoxin / Q000494:pharmacology; D014982:Xenopus laevis
D015222:Sodium Channels; D002104:Cadmium; D013779:Tetrodotoxin; D003545:Cysteine