INVESTIGATION OF LIGAND-BINDING SITES OF THE ACETYLCHOLINE-RECEPTOR USING PHOTOACTIVATABLE DERIVATIVES OF NEUROTOXIN-II FROM NAJA-NAJA-OXIANA

被引:43
作者
KREIENKAMP, HJ
UTKIN, YN
WEISE, C
MACHOLD, J
TSETLIN, VI
HUCHO, F
机构
[1] FREE UNIV BERLIN, INST BIOCHEM, THIELALLEE 63, W-1000 BERLIN 33, GERMANY
[2] MM SHEMYAKIN BIOORGAN CHEM INST, MOSCOW 117312, USSR
关键词
D O I
10.1021/bi00150a017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several photoaffinity derivatives of neurotoxin II from the venom of the central Asian cobra Naja naja oxiana have been prepared. After reaction of the I-125-labeled derivatives with the nicotinic acetylcholine receptor from electric organ, the alpha-subunit of the nAChR is almost exclusively labeled by the derivative carrying the photoactivatable group in position Lys46. In contrast to this, a reactive group at Lys26 predominantly labels the gamma- and delta-subunits, while the alpha- and beta-subunits incorporate much less radioactivity. Competition experiments with d-tubocurarine show that the gamma-subunit is labeled when this derivative occupies the high affinity d-tubocurarine-binding site, while the delta-subunit is labeled by the toxin bound at the low-affinity d-tubocurarine site. A model is discussed for the orientation of different loops of the toxin molecules in the binding site for agonists and competitive antagonists.
引用
收藏
页码:8239 / 8244
页数:6
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