© The Rockefeller University Press,
0021-9525/1999//493 $5.00
The Journal of Cell Biology, Volume 146, Number 2,
, 1999 493-500
Three-Dimensional Location of the Imperatoxin a Binding Site on the Ryanodine Receptor
Montserrat Samsóa,
Ramon Trujilloa,
Georgina B. Gurrolab,
Hector H. Valdiviab, and
Terence Wagenknechta,c
a Division of Molecular Medicine, Wadsworth Center, Albany, New York 12201-0509
b Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706
c Department of Biomedical Sciences, State University of New York, Albany, New York 12201
Wadsworth Center, Empire State Plaza, Albany, NY 12201-0509.(518) 474-7992(518) 474-6516
samso{at}wadsworth.org
Cryo-electron microscopy and three-dimensional, single-particle image analysis have been used to reveal the specific binding site of imperatoxin A (IpTxa) on the architecture of the calcium release channel/ryanodine receptor from skeletal muscle (RyR1). IpTxa is a peptide toxin that binds with high affinity to RyR1 and affects its functioning. The toxin was derivatized with biotin to enhance its detection with streptavidin. IpTxa binds to the cytoplasmic moiety of RyR1 between the clamp and handle domains, 11 nm away from the transmembrane pore. The proposed mimicry by IpTxa of the dihydropyridine receptor (DHPR) II-III loop, thought to be a main physiological excitation-contraction trigger, suggests that the IpTxa binding location is a potential excitation-contraction signal transduction site.
Key Words: ryanodine receptor • imperatoxin A • cryo-electron microscopy • three-dimensional reconstruction • excitation-contraction coupling
© 1999 The Rockefeller University Press
1.used in this paper: 2D, two-dimensional; 3D, three-dimensional; DHPR, dihydropyridine receptor; E-C, excitation-contraction; IpTxa, imperatoxin A; IpTxa-B, IpTxa-biotin conjugate; RyR, ryanodine receptor; RyR1, skeletal muscle isoform of the ryanodine receptor; SA, streptavidin; SR, sarcoplasmic reticulum; T tubule, transverse tubule
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