Critical Interactions at the Dimer Interface of -Bungarotoxin, a Neuronal Nicotinic Acetylcholine Receptor Antagonist
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- 作者：Gregory A. Grant ; Regina Al-Rabiee ; Xiao Lan Xu ; and Yueping Zhang
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：March 18, 1997
- 年：1997
- 卷：36
- 期：11
- 页码：3353 - 3358
- 全文大小：199K
- 年卷期：v.36,no.11(March 18, 1997)
- ISSN：1520-4995
文摘
The 
- and 
-neurotoxins are polypeptide antagonists ofnicotinic acetylcholine receptors derivedfrom snake venom. They are structurally very similar but differ intheir specificity for receptor subtypeand in their native aggregation state. While the -neurotoxinsare monomeric, the -neurotoxins occuras homodimers. The crystal structure shows that there is acorrelation in the distance between essentialarginine residues in the -bungarotoxin dimer and the distancebetween the acetylcholine binding sites inthe pentameric receptor. This has lead to an investigation of thecritical interactions at the dimer interfaceof -bungarotoxin. Mutations of residues that the crystalstructure indicates participate in dimer interactionwere found to fall into two general groups: those that do not affectthe dimerization state or activity of-bungarotoxin as single mutants, and those that interfere with it tosuch an extent that the protein is nolonger able to fold properly. In general, those residues that fallinto the latter group are found to beinvariant in -neurotoxins and not found in -neurotoxins. Theresults suggest that the extent of both themain chain-main chain 
-sheet hydrogen bond interaction and van derWaals interactions between Phe49 and Ile 20 are required for dimer formation. These studiesprovide a basis for understanding why the-neurotoxins readily dimerize in solution and the -neurotoxins donot and also suggest that there is apossible interrelationship between dimer formation and protein foldingin -bungarotoxin.
- and -neurotoxins are polypeptide antagonists ofnicotinic acetylcholine receptors derivedfrom snake venom. They are structurally very similar but differ intheir specificity for receptor subtypeand in their native aggregation state. While the -neurotoxinsare monomeric, the -neurotoxins occuras homodimers. The crystal structure shows that there is acorrelation in the distance between essentialarginine residues in the -bungarotoxin dimer and the distancebetween the acetylcholine binding sites inthe pentameric receptor. This has lead to an investigation of thecritical interactions at the dimer interfaceof -bungarotoxin. Mutations of residues that the crystalstructure indicates participate in dimer interactionwere found to fall into two general groups: those that do not affectthe dimerization state or activity of-bungarotoxin as single mutants, and those that interfere with it tosuch an extent that the protein is nolonger able to fold properly. In general, those residues that fallinto the latter group are found to beinvariant in -neurotoxins and not found in -neurotoxins. Theresults suggest that the extent of both themain chain-main chain -sheet hydrogen bond interaction and van derWaals interactions between Phe49 and Ile 20 are required for dimer formation. These studiesprovide a basis for understanding why the-neurotoxins readily dimerize in solution and the -neurotoxins donot and also suggest that there is apossible interrelationship between dimer formation and protein foldingin -bungarotoxin.