EurekaMag
+ Translate
+ Most Popular
Gaucher's disease;thirty-two years experience at Siriraj Hospital
A study of Macrobathra Meyrick from China (Lepidoptera, Cosmopterigidae)
First occurrence in ores of tetragonal chalcocite
Effects of trace element nutrition on sleep patterns in adult women
N.Z. range management guidelines. 2. Design of grazing management systems for tussock country
A case of lipoma of the esophagus
A revision of world Acanthosomatidae (Heteroptera: Pentatomidae): keys to and descriptions of subfamilies, tribes and genera, with designation of types
Life history of the coronate scyphozoan Linuche unguiculata (Swartz, 1788)
Perceptual restoration of obliterated sounds
Mutagenicity studies on two chromium(III) coordination compounds
The formation of the skeleton. I. Growth of a long bone. 1st appearance of a center of calcification
Leucopenia and abnormal liver function in travellers on malaria chemoprophylaxis
The joint commission: four key root causes loom large in sentinel event data
Treatment of vitiligo with topical 15% lactic acid solution in combination with ultra violet-A
Behaviour of dairy cows within three hours after feed supply: I. Influence of housing type and time elapsing after feed supply
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS)
The diet composition and nutritional knowledge of patients with anorexia nervosa
Physoporella croatica Herak, 1958 of the Slovak karst Anisian (Slovakia, the West Carpathians Mts.)
Bright lights, big noise. How effective are vehicle warning systems?
Ein Plesiosaurier-Rest mit Magensteinen aus mittlerem Lias von Quedlinburg
Incidence of Chlamydia trachomatis in patients with sterility
Monster soup: the microscope and Victorian fantasy
Preliminary tests with residual sprays against poultry lice
Duration of the life of plants in phylogeny

Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal 7 nicotinic receptor


Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal 7 nicotinic receptor



Journal of Biological Chemistry 272(39): 24279-24286



ISSN/ISBN: 0021-9258

DOI: 10.1074/jbc.272.39.24279

Long chain and short chain curaremimetic toxins from snakes possess 66-74 residues with five disulfide bonds and 60-62 residues with four disulfide bonds, respectively. Despite their structural differences all of these toxins bind with high affinity to the peripheral nicotinic acetylcholine receptors (AChR). Binding experiments have now revealed that long chain toxins only, like the neuronal kappa-bungarotoxin, have a high affinity for a chimeric form of the neuronal alpha-7 receptor, with K-d values ranging from about 1 to 12 nM. In contrast, all other toxins bind to the chimeric a7 receptor with a low affinity, with K-d values ranging between 3 and 22 mu-M. These results are supported by electrophysiological recordings on both the wild-type and chimeric alpha-7 receptors. Amino acid sequence analyses have suggested that high affinities for the neuronal receptor are associated with the presence of the fifth disulfide at the tip of the toxin second loop. In agreement with this conclusion, we show that a long chain toxin whose fifth disulfide is reduced and then dithiopyridylated has a low affinity (K-d = 12 mu-M) for the neuronal alpha-7 receptor, whereas it retains a high affinity (K-d = 0.35 nM) for the peripheral AChR. Thus, a long chain curaremimetic toxin having a reduced fifth disulfide bond behaves like a short chain toxin toward both the peripheral and neuronal AChR. Therefore, functional classification of toxins that bind to AChRs should probably be done by considering their activities on both peripheral and neuronal receptors.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 021495009

Download citation: RISBibTeXText

Related references

Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. Journal of Biological Chemistry 272(39): 24279-24286, 1997

How do snake curaremimetic toxins discriminate between nicotinic acetylcholine receptor subtypes. Toxicology Letters (Shannon) 102-103: 199-203, 1998

How do snake curaremimetic toxins discriminate between nicotinic acetylcholine receptor subtypes. Toxicology Letters 102-103: 199-203, 1998

The molecular basis of curaremimetic snake neurotoxin specificity for neuronal nicotinic receptor subtypes. Journal of Toxicology Toxin Reviews 12(2): 105-153, 1993

Relative spatial position of a snake neurotoxin and the reduced disulfide bond a(Cys192-Cys193) at the ac interface of the nicotinic acetylcholine receptor. The Journal of Biological Chemistry 275(33): 608-15, 2000

α-Elapitoxin-Aa2a, a long-chain snake α-neurotoxin with potent actions on muscle (α1)(2)βγδ nicotinic receptors, lacks the classical high affinity for neuronal α7 nicotinic receptors. Biochemical Pharmacology 81(2): 314-325, 2011

Interaction of protein ligands with receptor fragments. On the residues of curaremimetic toxins that recognize fragments 128-142 and 185-199 of the alpha-subunit of the nicotinic acetylcholine receptor. Febs Letters 338(3): 331-338, 1994

Transfer of a b-hairpin from the functional site of snake curaremimetic toxins to the a/b scaffold of scorpion toxins: three-dimensional solution structure of the chimeric protein. Biochemistry (American Chemical Society) 35: 35-43, 1996

Relative spatial position of a snake neurotoxin and the reduced disulfide bond alpha (Cys192-Cys193) at the alpha gamma interface of the nicotinic acetylcholine receptor. Journal of Biological Chemistry 275(33): 25608-25615, 2000

Insecticidal spider toxins are high affinity positive allosteric modulators of the nicotinic acetylcholine receptor. Febs Letters 593(12): 1336-1350, 2019

Transfer of a beta-hairpin from the functional site of snake curaremimetic toxins to the alpha/beta scaffold of scorpion toxins: three-dimensional solution structure of the chimeric protein. Biochemistry 35(26): 8535-8543, 1996

ABT-594 is a high-affinity, selective neuronal nicotinic acetylcholine receptor radioligand. Society for Neuroscience Abstracts 24(1-2): 85, 1998

3-Pyridyl ethers as novel high affinity neuronal nicotinic acetylcholine receptor ligands. Society for Neuroscience Abstracts 21(1-3): 605, 1995

Structural aspects of high affinity ligands for the alpha 4 beta 2 neuronal nicotinic receptor. Pharmaceutica Acta Helvetiae 74(2-3): 115-123, 2000

Binding properties of A-85380, a high-affinity neuronal nicotinic acetylcholine receptor radioligand. Society for Neuroscience Abstracts 21(1-3): 606, 1995