General Information of This Target
Target ID
BTDT00032
Target Name
Acetylcholine receptor subunit alpha (CHRNA1)
Target Bioclass
Receptor
Uniprot ID
P02711
3D Structure
Download
2D Sequence
3D Structure
Source
Predict by Alphafold2
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Alphafold Parameters: msa_mode: mmseqs2_uniref_env model_type: auto num_recycles: auto
Gene Name
CHRNA1
Sequence
MILCSYWHVGLVLLLFSCCGLVLGSEHETRLVANLLENYNKVIRPVEHHTHFVDITVGLQ
LIQLINVDEVNQIVETNVRLRQQWIDVRLRWNPADYGGIKKIRLPSDDVWLPDLVLYNNA
DGDFAIVHMTKLLLDYTGKIMWTPPAIFKSYCEIIVTHFPFDQQNCTMKLGIWTYDGTKV
SISPESDRPDLSTFMESGEWVMKDYRGWKHWVYYTCCPDTPYLDITYHFIMQRIPLYFVV
NVIIPCLLFSFLTVLVFYLPTDSGEKMTLSISVLLSLTVFLLVIVELIPSTSSAVPLIGK
YMLFTMIFVISSIIVTVVVINTHHRSPSTHTMPQWVRKIFINTIPNVMFFSTMKRASKEK
QENKIFADDIDISDISGKQVTGEVIFQTPLIKNPDVKSAIEGVKYIAEHMKSDEESSNAA
EEWKYVAMVIDHILLCVFMLICIIGTVSVFAGRLIELSQEG

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Family
the ligand-gated ion channel (TC 1.A.9) family
Function
Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

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Taxonomy ID
7788
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Chondrichthyes
Order: Torpediniformes
Family: Torpedinidae
Genus: Torpedo
Species: Torpedo marmorata
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Short neurotoxin 1 Dissociation constant
0.07 nM
[1], [2], [3]
 Toxin Info    Erabutoxin b Dissociation constant
0.07 nM
[1- 15]
 Toxin Info    Erabutoxin c Dissociation constant
0.14 nM
[5- 17]
 Toxin Info    Alpha-bungarotoxin Dissociation constant
0.4 nM
[1- 39]
 Toxin Info    Alpha-bungarotoxin, isoform A31 Dissociation constant
0.4 nM
[40], [41]
 Toxin Info    Erabutoxin a Dissociation constant
21 μM
[1- 48]
 Toxin Info    Alpha-conotoxin EIIA Inhibition constant
0.46 nM
[49], [50], [51]
 Toxin Info    Alpha-conotoxin EIIB Inhibition constant
0.7 nM
[52], [51]
 Toxin Info    Alpha-conotoxin EIIA Inhibition constant
105 nM
[49], [50], [51]
References
Ref 1 Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. doi: 10.1074/jbc.272.39.24279.
Ref 2 Three-dimensional solution structure of a curaremimetic toxin from Naja nigricollis venom: a proton NMR and molecular modeling study. Biochemistry. 1992 Nov 24;31(46):11335-47. doi: 10.1021/bi00161a011.
Ref 3 Motions and structural variability within toxins: implication for their use as scaffolds for protein engineering. Protein Sci. 2003 Feb;12(2):266-77. doi: 10.1110/ps.0227703.
Ref 4 Sequence analysis of a cDNA encoding a erabutoxin b from the sea-snake Laticauda semifasciata. Nucleic Acids Res. 1989 Dec 25;17(24):10490. doi: 10.1093/nar/17.24.10490.
Ref 5 Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences. Gene. 2003 Aug 14;313:111-8. doi: 10.1016/s0378-1119(03)00637-1.
Ref 6 The amino acid sequences of erabutoxins, neurotoxic proteins of sea-snake (Laticauda semifasciata) venom. Biochem J. 1971 May;122(4):453-61. doi: 10.1042/bj1220453.
Ref 7 Correction of partial amino acid sequence of erabutoxins. Biochem J. 1977 Oct 1;167(1):289-91. doi: 10.1042/bj1670289.
Ref 8 Protein sequencing by computer graphics. Biochim Biophys Acta. 1977 Apr 25;491(2):605-8. doi: 10.1016/0005-2795(77)90309-9.
Ref 9 Genetic engineering of snake toxins. The functional site of Erabutoxin a, as delineated by site-directed mutagenesis, includes variant residues. J Biol Chem. 1995 Apr 21;270(16):9362-9. doi: 10.1074/jbc.270.16.9362.
Ref 10 The crystal structure of a post-synaptic neurotoxin from sea snake at A resolution. FEBS Lett. 1976 Sep 15;68(1):1-4. doi: 10.1016/0014-5793(76)80390-0.
Ref 11 Structure and function of snake venom curarimimetic neurotoxins. Mol Pharmacol. 1978 Jul;14(4):710-6.
Ref 12 Molecular conformation of erabutoxin b; atomic coordinates at 2.5 A resolution. Biochem Biophys Res Commun. 1979 Jun 13;88(3):950-9. doi: 10.1016/0006-291x(79)91500-6.
Ref 13 Erabutoxin b. Structure/function relationships following initial protein refinement at 0.140-nm resolution. Eur J Biochem. 1986 Dec 15;161(3):579-87. doi: 10.1111/j.1432-1033.1986.tb10481.x.
Ref 14 Structure determination of a dimeric form of erabutoxin-b, crystallized from a thiocyanate solution. Acta Crystallogr B. 1992 Aug 1;48 ( Pt 4):520-31. doi: 10.1107/s010876819200096x.
Ref 15 Tertiary structure of erabutoxin b in aqueous solution as elucidated by two-dimensional nuclear magnetic resonance. J Mol Biol. 1994 Jul 8;240(2):155-66. doi: 10.1006/jmbi.1994.1429.
Ref 16 Structure of the snake short-chain neurotoxin, erabutoxin c, precursor gene. Eur J Biochem. 1990 Nov 13;193(3):629-33. doi: 10.1111/j.1432-1033.1990.tb19380.x.
Ref 17 The isolation, properties and amino acid sequence of erabutoxin c, a minor neurotoxic component of the venom of a sea snake Katicauda semifasciata. Biochem J. 1972 Nov;130(2):547-55. doi: 10.1042/bj1300547.
Ref 18 Genetic characterization of the mRNAs encoding alpha-bungarotoxin: isoforms and RNA editing in Bungarus multicinctus gland cells. Nucleic Acids Res. 1998 Dec 15;26(24):5624-9. doi: 10.1093/nar/26.24.5624.
Ref 19 Genetic organization of alpha-bungarotoxins from Bungarus multicinctus (Taiwan banded krait): evidence showing that the production of alpha-bungarotoxin isotoxins is not derived from edited mRNAs. Nucleic Acids Res. 1999 Oct 15;27(20):3970-5. doi: 10.1093/nar/27.20.3970.
Ref 20 Purification, properties and amino acid sequence of -bungarotoxin from the venom of Bungarus multicinctus. Hoppe Seylers Z Physiol Chem. 1972 Feb;353(2):243-62. doi: 10.1515/bchm2.1972.353.1.243.
Ref 21 Primary structure of alpha-bungarotoxin. Six amino acid residues differ from the previously reported sequence. FEBS Lett. 1987 Sep 28;222(1):79-82. doi: 10.1016/0014-5793(87)80195-3.
Ref 22 Isolation of antigenically reactive peptide fragments and localization of antigenic regions of alpha-bungarotoxin. Biochem Biophys Res Commun. 1988 Sep 15;155(2):870-6. doi: 10.1016/s0006-291x(88)80576-x.
Ref 23 cDNA sequence analysis and expression of alpha-bungarotoxin from Taiwan banded krait (Bungarus multicinctus). Biochem Biophys Res Commun. 1995 Nov 22;216(3):1088-94. doi: 10.1006/bbrc.1995.2732.
Ref 24 Structural studies of alpha-bungarotoxin. 3. Corrections in the primary sequence and X-ray structure and characterization of an isotoxic alpha-bungarotoxin. Biochemistry. 1988 Apr 19;27(8):2775-81. doi: 10.1021/bi00408a018.
Ref 25 Neutralizing monoclonal antibody specific for alpha-bungarotoxin: preparation and characterization of the antibody, and localization of antigenic region of alpha-bungarotoxin. FEBS Lett. 1989 Aug 28;254(1-2):106-10. doi: 10.1016/0014-5793(89)81018-x.
Ref 26 Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo. Neurochem Int. 1998 Oct;33(4):307-12. doi: 10.1016/s0197-0186(98)00033-3.
Ref 27 The cholinergic antagonist alpha-bungarotoxin also binds and blocks a subset of GABA receptors. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5149-54. doi: 10.1073/pnas.0600847103. Epub 2006 Mar 20.
Ref 28 Neurotoxins from snake venoms and -conotoxin ImI inhibit functionally active ionotropic -aminobutyric acid (GABA) receptors. J Biol Chem. 2015 Sep 11;290(37):22747-58. doi: 10.1074/jbc.M115.648824. Epub 2015 Jul 28.
Ref 29 Snake neurotoxin -bungarotoxin is an antagonist at native GABA(A) receptors. Neuropharmacology. 2015 Jun;93:28-40. doi: 10.1016/j.neuropharm.2015.01.001. Epub 2015 Jan 26.
Ref 30 The crystal structure of alpha-bungarotoxin at 2.5 A resolution: relation to solution structure and binding to acetylcholine receptor. Protein Eng. 1986 Oct-Nov;1(1):37-46. doi: 10.1093/protein/1.1.37.
Ref 31 Structural studies of alpha-bungarotoxin. 1. Sequence-specific 1H NMR resonance assignments. Biochemistry. 1988 Apr 19;27(8):2763-71. doi: 10.1021/bi00408a016.
Ref 32 Structural studies of alpha-bungarotoxin. 2. 1H NMR assignments via an improved relayed coherence transfer nuclear overhauser enhancement experiment. Biochemistry. 1988 Apr 19;27(8):2772-5. doi: 10.1021/bi00408a017.
Ref 33 NMR solution structure of an alpha-bungarotoxin/nicotinic receptor peptide complex. Biochemistry. 1993 Nov 23;32(46):12290-8. doi: 10.1021/bi00097a004.
Ref 34 Three-dimensional solution structure of the complex of alpha-bungarotoxin with a library-derived peptide. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6059-64. doi: 10.1073/pnas.94.12.6059.
Ref 35 The solution structure of the complex formed between alpha-bungarotoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica. J Biol Chem. 2001 Jun 22;276(25):22930-40. doi: 10.1074/jbc.M102300200. Epub 2001 Apr 18.
Ref 36 A beta -hairpin structure in a 13-mer peptide that binds alpha -bungarotoxin with high affinity and neutralizes its toxicity. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6629-34. doi: 10.1073/pnas.111164298. Epub 2001 May 29.
Ref 37 NMR structure of alpha-bungarotoxin free and bound to a mimotope of the nicotinic acetylcholine receptor. Biochemistry. 2002 Feb 5;41(5):1457-63. doi: 10.1021/bi011012f.
Ref 38 NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor. J Biol Chem. 2002 Apr 5;277(14):12406-17. doi: 10.1074/jbc.M110320200. Epub 2002 Jan 14.
Ref 39 The mechanism for acetylcholine receptor inhibition by alpha-neurotoxins and species-specific resistance to alpha-bungarotoxin revealed by NMR. Neuron. 2002 Jul 18;35(2):319-32. doi: 10.1016/s0896-6273(02)00773-0.
Ref 40 Identification of alpha-bungarotoxin (A31) as the major postsynaptic neurotoxin, and complete nucleotide identity of a genomic DNA of Bungarus candidus from Java with exons of the Bungarus multicinctus alpha-bungarotoxin (A31) gene. Toxicon. 2003 Sep 15;42(4):381-90. doi: 10.1016/s0041-0101(03)00168-5.
Ref 41 Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors. Biochem J. 2019 Apr 26;476(8):1285-1302. doi: 10.1042/BCJ20180909.
Ref 42 Cloning and sequence analysis of the cDNA encoding a snake neurotoxin precursor. Biochimie. 1985 Feb;67(2):185-9. doi: 10.1016/s0300-9084(85)80046-8.
Ref 43 The disulphide bonds of erabutoxin a, a neurotoxic protein of a sea-snake (Laticauda semifasciata) venom. Biochem J. 1971 May;122(4):463-7. doi: 10.1042/bj1220463.
Ref 44 Genetic engineering of snake toxins. Role of invariant residues in the structural and functional properties of a curaremimetic toxin, as probed by site-directed mutagenesis. J Biol Chem. 1993 Jan 15;268(2):909-16.
Ref 45 Three-dimensional structure of neurotoxin a from venom of the Philippines sea snake. Proc Natl Acad Sci U S A. 1977 Mar;74(3):971-4. doi: 10.1073/pnas.74.3.971.
Ref 46 The crystal structure of erabutoxin a at 2.0-A resolution. J Biol Chem. 1989 Jun 5;264(16):9239-42. doi: 10.2210/pdb5ebx/pdb.
Ref 47 Structure of dimeric and monomeric erabutoxin a refined at 1.5 A resolution. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):964-74. doi: 10.1107/s0907444998005125.
Ref 48 High resolution x-ray analysis of two mutants of a curaremimetic snake toxin. Eur J Biochem. 2000 Mar;267(5):1323-9. doi: 10.1046/j.1432-1327.2000.01099.x.
Ref 49 Evolution of Conus peptide genes: duplication and positive selection in the A-superfamily. J Mol Evol. 2010 Feb;70(2):190-202. doi: 10.1007/s00239-010-9321-7. Epub 2010 Feb 9.
Ref 50 Identification and functional characterization of a novel -conotoxin (EIIA) from Conus ermineus. Anal Bioanal Chem. 2013 Jun;405(15):5341-51. doi: 10.1007/s00216-013-6926-x. Epub 2013 Apr 14.
Ref 51 Discovery and characterization of EII(B,) a new -conotoxin from Conus ermineus venom by nAChRs affinity capture monitored by MALDI-TOF/TOF mass spectrometry. Toxicon. 2017 May;130:1-10. doi: 10.1016/j.toxicon.2017.02.023. Epub 2017 Feb 24.
Ref 52 Conotoxin Diversity in Chelyconus ermineus (Born, 1778) and the Convergent Origin of Piscivory in the Atlantic and Indo-Pacific Cones. Genome Biol Evol. 2018 Oct 1;10(10):2643-2662. doi: 10.1093/gbe/evy150.
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