A MOLECULAR BLUEPRINT FOR THE PORE-FORMING STRUCTURE OF VOLTAGE-GATED CALCIUM CHANNELS

被引:73
作者
GROVE, A
TOMICH, JM
MONTAL, M
机构
[1] UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093
[2] UNIV CALIF SAN DIEGO,DEPT PHYS,LA JOLLA,CA 92093
[3] UNIV SO CALIF,SCH MED,DEPT BIOCHEM,LOS ANGELES,CA 90033
[4] CHILDRENS HOSP,LOS ANGELES,CA 90054
关键词
DRUG; LIPID BILAYERS; MOLECULAR MODELING; 4-HELIX BUNDLE;
D O I
10.1073/pnas.88.15.6418
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
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.
引用
收藏
页码:6418 / 6422
页数:5
相关论文
共 35 条
  • [1] PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF A HIGH-VOLTAGE ACTIVATED CALCIUM-CHANNEL FROM RABBIT LUNG
    BIEL, M
    RUTH, P
    BOSSE, E
    HULLIN, R
    STUHMER, W
    FLOCKERZI, V
    HOFMANN, F
    [J]. FEBS LETTERS, 1990, 269 (02) : 409 - 412
  • [2] BOLGER GT, 1987, J PHARMACOL EXP THER, V240, P922
  • [3] CATTERALL WA, 1988, J BIOL CHEM, V263, P3535
  • [4] 3-DIMENSIONAL STRUCTURE OF MEMBRANE AND SURFACE-PROTEINS
    EISENBERG, D
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1984, 53 : 595 - 623
  • [5] SEQUENCE AND EXPRESSION OF MESSENGER-RNAS ENCODING THE ALPHA-1-SUBUNIT AND ALPHA-2-SUBUNIT OF A DHP-SENSITIVE CALCIUM-CHANNEL
    ELLIS, SB
    WILLIAMS, ME
    WAYS, NR
    BRENNER, R
    SHARP, AH
    LEUNG, AT
    CAMPBELL, KP
    MCKENNA, E
    KOCH, WJ
    HUI, A
    SCHWARTZ, A
    HARPOLD, MM
    [J]. SCIENCE, 1988, 241 (4873) : 1661 - 1664
  • [6] THE STRUCTURE OF THE VOLTAGE-SENSITIVE SODIUM-CHANNEL - INFERENCES DERIVED FROM COMPUTER-AIDED ANALYSIS OF THE ELECTROPHORUS-ELECTRICUS CHANNEL PRIMARY STRUCTURE
    GREENBLATT, RE
    BLATT, Y
    MONTAL, M
    [J]. FEBS LETTERS, 1985, 193 (02) : 125 - 134
  • [7] GROVE A, 1990, Society for Neuroscience Abstracts, V16, P957
  • [8] HESS P, 1990, ANNU REV NEUROSCI, V13, P337, DOI 10.1146/annurev.neuro.13.1.337
  • [9] CALCIUM-CHANNEL SELECTIVITY FOR DIVALENT AND MONO-VALENT CATIONS - VOLTAGE AND CONCENTRATION-DEPENDENCE OF SINGLE CHANNEL CURRENT IN VENTRICULAR HEART-CELLS
    HESS, P
    LANSMAN, JB
    TSIEN, RW
    [J]. JOURNAL OF GENERAL PHYSIOLOGY, 1986, 88 (03) : 293 - 319
  • [10] PRIMARY STRUCTURE OF THE GAMMA-SUBUNIT OF THE DHP-SENSITIVE CALCIUM-CHANNEL FROM SKELETAL-MUSCLE
    JAY, SD
    ELLIS, SB
    MCCUE, AF
    WILLIAMS, ME
    VEDVICK, TS
    HARPOLD, MM
    CAMPBELL, KP
    [J]. SCIENCE, 1990, 248 (4954) : 490 - 492