A STRUCTURAL MOTIF FOR THE VOLTAGE-GATED POTASSIUM CHANNEL PORE

被引:42
作者
LIPKIND, GM
HANCK, DA
FOZZARD, HA
机构
[1] UNIV CHICAGO, DEPT BIOCHEM & MOLEC BIOL, CHICAGO, IL 60637 USA
[2] UNIV CHICAGO, DEPT MED, CHICAGO, IL 60637 USA
[3] UNIV CHICAGO, DEPT PHARMACOL & PHYSIOL SCI, CHICAGO, IL 60637 USA
关键词
D O I
10.1073/pnas.92.20.9215
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mutation studies have identified a region of the S5-S6 loop of voltage-gated K+ channels (P region) responsible for tetraethylammonium (TEA) block and permeation/selectivity properties. We previously modeled a similar region of the Na+ channel as four beta-hairpins with the C strands from each of the domains forming the external vestibule and with charged residues at the beta-turns forming the selectivity filter, However, the K+ channel P region amino acid composition is much more hydrophobic in this area. Here we propose a structural motif for the K+ channel pore based on the following postulates (Kv2.1 numbering). (i) The external TEA binding site is formed by four Tyr-380 residues; P loop residues participating in the internal TEA binding site are four Met-371 and Thr-372 residues. (ii) P regions form extended hairpins with beta-turns in sequence ITMT. (iii) Only C ends of hairpins form the inner walls of the pore. (iv) They are extended nonregular strands with backbone carbonyl oxygens of segment VGYGD facing the pore with the conformation BRLRL. (v) Juxtaposition of P loops of the four subunits forms the pore. Fitting the external and internal TEA sites to TEA molecules predicts an hourglass-like pore with the narrowest point (GYG) as wide as 5.5 Angstrom, suggesting that selectivity may be achieved by interactions of carbonyls with partially hydrated K+. Other potential cation binding sites also exist in the pore.
引用
收藏
页码:9215 / 9219
页数:5
相关论文
共 49 条
[1]  
AIYAR J, 1995, BIOPHYS J, V68, P23
[2]  
[Anonymous], 1993, PROTEINS STRUCTURES
[3]   AN SS1-SS2 BETA-BARREL STRUCTURE FOR THE VOLTAGE-ACTIVATED POTASSIUM CHANNEL [J].
BOGUSZ, S ;
BOXER, A ;
BUSATH, DD .
PROTEIN ENGINEERING, 1992, 5 (04) :285-293
[4]   FUNCTIONAL BASES FOR INTERPRETING AMINO-ACID-SEQUENCES OF VOLTAGE-DEPENDENT K+-CHANNELS [J].
BROWN, AM .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 1993, 22 :173-198
[5]  
BURLEY SK, 1988, ADV PROTEIN CHEM, V39, P125
[6]   PERMEATION OF NA+ THROUGH A DELAYED RECTIFIER K+ CHANNEL IN CHICK DORSAL-ROOT GANGLION NEURONS [J].
CALLAHAN, MJ ;
KORN, SJ .
JOURNAL OF GENERAL PHYSIOLOGY, 1994, 104 (04) :747-771
[7]  
CHANDY KG, 1995, HDB RECEPTORS CHANNE, P1
[8]   THE INTERNAL QUATERNARY AMMONIUM RECEPTOR-SITE OF SHAKER POTASSIUM CHANNELS [J].
CHOI, KL ;
MOSSMAN, C ;
AUBE, J ;
YELLEN, G .
NEURON, 1993, 10 (03) :533-541
[9]   HISTIDINE SUBSTITUTION IDENTIFIES A SURFACE POSITION AND CONFERS CS+ SELECTIVITY ON A K+ PORE [J].
DEBIASI, M ;
DREWE, JA ;
KIRSCH, GE ;
BROWN, AM .
BIOPHYSICAL JOURNAL, 1993, 65 (03) :1235-1242
[10]   ACETYLCHOLINE BINDING BY A SYNTHETIC RECEPTOR - IMPLICATIONS FOR BIOLOGICAL RECOGNITION [J].
DOUGHERTY, DA ;
STAUFFER, DA .
SCIENCE, 1990, 250 (4987) :1558-1560