spacer
spacer

PDBsum entry 1hc9
Go to PDB code: 
protein metals Protein-protein interface(s) links
Toxin/peptide PDB id
1hc9

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
74 a.a. *
74 a.a. *
13 a.a. *
12 a.a. *
Metals
IOD ×2
Waters ×217
* Residue conservation analysis
PDB id:
1hc9
Name: Toxin/peptide
Title: Alpha-bungarotoxin complexed with high affinity peptide
Structure: Alpha-bungarotoxin isoform v31. Chain: a. Synonym: alpha-btx v31, alpha-bgt(v31), bgtx v31, long neurotoxin 1. Other_details: alpha-neurotoxin. Alpha-bungarotoxin isoform a31. Chain: b. Synonym: alpha-btx a31, alpha-bgt(a31), bgtx a31, long neurotoxin 1. Peptide inhibitor. Chain: c, d.
Source: Bungarus multicinctus. Many-banded krait. Organism_taxid: 8616. Secretion: venom. Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Other_details: mimotope of the nicotinic acetylcholine receptor
Biol. unit: Hetero-Dimer (from PDB file)
Resolution:
1.80Å     R-factor:   0.202     R-free:   0.235
Authors: M.Harel,R.Kasher,J.L.Sussman
Key ref:
M.Harel et al. (2001). The binding site of acetylcholine receptor as visualized in the X-Ray structure of a complex between alpha-bungarotoxin and a mimotope peptide. Neuron, 32, 265-275. PubMed id: 11683996 DOI: 10.1016/S0896-6273(01)00461-5
Date:
02-May-01     Release date:   10-Nov-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P60616  (3L21V_BUNMU) -  Alpha-bungarotoxin isoform V31 from Bungarus multicinctus
Seq:
Struc: 		95 a.a.
74 a.a.
Protein chain
P60615  (3L21A_BUNMU) -  Alpha-bungarotoxin from Bungarus multicinctus
Seq:
Struc: 		95 a.a.
74 a.a.
Protein chain
No UniProt id for this chain
Struc: 13 a.a.
Protein chain
No UniProt id for this chain
Struc: 12 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1016/S0896-6273(01)00461-5 Neuron 32:265-275 (2001)
PubMed id: 11683996  
 
 
The binding site of acetylcholine receptor as visualized in the X-Ray structure of a complex between alpha-bungarotoxin and a mimotope peptide.
M.Harel, R.Kasher, A.Nicolas, J.M.Guss, M.Balass, M.Fridkin, A.B.Smit, K.Brejc, T.K.Sixma, E.Katchalski-Katzir, J.L.Sussman, S.Fuchs.
 
  ABSTRACT  
 
We have determined the crystal structure at 1.8 A resolution of a complex of alpha-bungarotoxin with a high affinity 13-residue peptide that is homologous to the binding region of the alpha subunit of acetylcholine receptor. The peptide fits snugly to the toxin and adopts a beta hairpin conformation. The structures of the bound peptide and the homologous loop of acetylcholine binding protein, a soluble analog of the extracellular domain of acetylcholine receptor, are remarkably similar. Their superposition indicates that the toxin wraps around the receptor binding site loop, and in addition, binds tightly at the interface of two of the receptor subunits where it inserts a finger into the ligand binding site, thus blocking access to the acetylcholine binding site and explaining its strong antagonistic activity.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. A Stereo View of the Combined Model of α-BTX-HAP (Red) and AChBP Structure with Subunit A in Green and Subunit B in Yellow Showing the Insertion of Loop 2 of the Toxin into the Interface of the Two SubunitsThe positively charged HEPES molecule (black stick figure) shows the location of the acetylcholine binding site and the blockage of passage to this site caused by the binding of the toxin. The HAP, which overlaps the 182–193 loop of AChBP, is shown in blue 		Figure 7.
Figure 7. The Combined Model of the AChBP Pentamer with Five Copies of α-BTX (Red) Bound to It, as Viewed down the 5-Fold Axis of the Pentamer
 
  The above figures are reprinted by permission from Cell Press: Neuron (2001, 32, 265-275) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20139708 L.Moise, J.Liu, E.Pryazhnikov, L.Khiroug, A.Jeromin, and E.Hawrot (2010).
K(V)4.2 channels tagged in the S1-S2 loop for alpha-bungarotoxin binding provide a new tool for studies of channel expression and localization.
  Channels (Austin), 4, 115-123.  
20204665 M.Parthiban, P.Shanmughavel, and R.Sowdhamini (2010).
In silico point mutation and evolutionary trace analysis applied to nicotinic acetylcholine receptors in deciphering ligand-binding surfaces.
  J Mol Model, 16, 1651-1670.  
  19210780 A.Nasiripourdori, B.Ranjbar, and H.Naderi-Manesh (2009).
Binding of long-chain alpha-neurotoxin would stabilize the resting state of nAChR: a comparative study with alpha-conotoxin.
  Theor Biol Med Model, 6, 3.  
19603113 D.L.Minor (2009).
Searching for interesting channels: pairing selection and molecular evolution methods to study ion channel structure and function.
  Mol Biosyst, 5, 802-810.  
19715355 M.Sanghvi, A.K.Hamouda, M.I.Davis, R.A.Morton, S.Srivastava, A.Pandhare, P.K.Duddempudi, T.K.Machu, D.M.Lovinger, J.B.Cohen, and M.P.Blanton (2009).
Hydrophobic photolabeling studies identify the lipid-protein interface of the 5-HT3A receptor.
  Biochemistry, 48, 9278-9286.  
18485004 A.Galat, G.Gross, P.Drevet, A.Sato, and A.Ménez (2008).
Conserved structural determinants in three-fingered protein domains.
  FEBS J, 275, 3207-3225.  
18812318 M.E.Wilkins, X.Li, and T.G.Smart (2008).
Tracking Cell Surface GABAB Receptors Using an {alpha}-Bungarotoxin Tag.
  J Biol Chem, 283, 34745-34752.  
18607650 W.H.Bisson, G.Westera, P.A.Schubiger, and L.Scapozza (2008).
Homology modeling and dynamics of the extracellular domain of rat and human neuronal nicotinic acetylcholine receptor subtypes alpha4beta2 and alpha7.
  J Mol Model, 14, 891-899.  
17643119 C.D.Dellisanti, Y.Yao, J.C.Stroud, Z.Z.Wang, and L.Chen (2007).
Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution.
  Nat Neurosci, 10, 953-962.
PDB code: 2qc1
17651090 D.Kalamida, K.Poulas, V.Avramopoulou, E.Fostieri, G.Lagoumintzis, K.Lazaridis, A.Sideri, M.Zouridakis, and S.J.Tzartos (2007).
Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity.
  FEBS J, 274, 3799-3845.  
17576769 E.N.Lyukmanova, Z.O.Shenkarev, A.A.Schulga, Y.S.Ermolyuk, D.Y.Mordvintsev, Y.N.Utkin, M.A.Shoulepko, R.C.Hogg, D.Bertrand, D.A.Dolgikh, V.I.Tsetlin, and M.P.Kirpichnikov (2007).
Bacterial expression, NMR, and electrophysiology analysis of chimeric short/long-chain alpha-neurotoxins acting on neuronal nicotinic receptors.
  J Biol Chem, 282, 24784-24791.  
17307283 Y.Cheng, J.K.Suen, Z.Radić, S.D.Bond, M.J.Holst, and J.A.McCammon (2007).
Continuum simulations of acetylcholine diffusion with reaction-determined boundaries in neuromuscular junction models.
  Biophys Chem, 127, 129-139.  
16637282 I.E.Kasheverov, I.u.N.Utkin, and V.I.Tsetlin (2006).
[Natural alpha-conotoxins and their synthetic analogues in studies of nicotinic acetylcholine receptors]
  Bioorg Khim, 32, 115-129.  
16086595 A.O.Samson, J.H.Chill, and J.Anglister (2005).
Two-dimensional measurement of proton T1rho relaxation in unlabeled proteins: mobility changes in alpha-bungarotoxin upon binding of an acetylcholine receptor peptide.
  Biochemistry, 44, 10926-10934.  
15864502 C.Peter, A.Korngreen, and V.Witzemann (2005).
Mutation of single murine acetylcholine receptor subunits reveals differential contribution of P121 to acetylcholine binding and channel opening.
  Pflugers Arch, 450, 178-184.  
15579462 I.Putrenko, M.Zakikhani, and J.A.Dent (2005).
A family of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans.
  J Biol Chem, 280, 6392-6398.  
15729554 M.Assadi, and M.Müntener (2005).
Utrophin is lacking at the neuromuscular junctions in the extraocular muscles of normal cat: artefact or true?
  Histochem Cell Biol, 123, 189-194.  
15899893 P.H.Celie, R.V.Klaassen, S.E.van Rossum-Fikkert, R.van Elk, P.van Nierop, A.B.Smit, and T.K.Sixma (2005).
Crystal structure of acetylcholine-binding protein from Bulinus truncatus reveals the conserved structural scaffold and sites of variation in nicotinic acetylcholine receptors.
  J Biol Chem, 280, 26457-26466.
PDB code: 2bj0
15791209 Y.Bourne, T.T.Talley, S.B.Hansen, P.Taylor, and P.Marchot (2005).
Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors.
  EMBO J, 24, 1512-1522.
PDB code: 1yi5
15117947 R.E.Hibbs, T.T.Talley, and P.Taylor (2004).
Acrylodan-conjugated cysteine side chains reveal conformational state and ligand site locations of the acetylcholine-binding protein.
  J Biol Chem, 279, 28483-28491.  
15182348 S.Dutertre, and R.J.Lewis (2004).
Computational approaches to understand alpha-conotoxin interactions at neuronal nicotinic receptors.
  Eur J Biochem, 271, 2327-2334.  
14745112 S.Nirthanan, and M.C.Gwee (2004).
Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on.
  J Pharmacol Sci, 94, 1.  
15448163 T.Sanders, and E.Hawrot (2004).
A novel pharmatope tag inserted into the beta4 subunit confers allosteric modulation to neuronal nicotinic receptors.
  J Biol Chem, 279, 51460-51465.  
15252034 X.Lou, Q.Liu, X.Tu, J.Wang, M.Teng, L.Niu, D.J.Schuller, Q.Huang, and Q.Hao (2004).
The atomic resolution crystal structure of atratoxin determined by single wavelength anomalous diffraction phasing.
  J Biol Chem, 279, 39094-39104.
PDB codes: 1v6p 1vb0
15563595 Y.Sekine-Aizawa, and R.L.Huganir (2004).
Imaging of receptor trafficking by using alpha-bungarotoxin-binding-site-tagged receptors.
  Proc Natl Acad Sci U S A, 101, 17114-17119.  
12850210 H.Jingami, S.Nakanishi, and K.Morikawa (2003).
Structure of the metabotropic glutamate receptor.
  Curr Opin Neurobiol, 13, 271-278.  
12885641 H.S.Young, L.G.Herbette, and V.Skita (2003).
Alpha-bungarotoxin binding to acetylcholine receptor membranes studied by low angle X-ray diffraction.
  Biophys J, 85, 943-953.  
14592862 J.M.Lindstrom (2003).
Nicotinic acetylcholine receptors of muscles and nerves: comparison of their structures, functional roles, and vulnerability to pathology.
  Ann N Y Acad Sci, 998, 41-52.  
12770823 L.Lozzi, B.Lelli, Y.Runci, S.Scali, A.Bernini, C.Falciani, A.Pini, N.Niccolai, P.Neri, and L.Bracci (2003).
Rational design and molecular diversity for the construction of anti-alpha-bungarotoxin antidotes with high affinity and in vivo efficiency.
  Chem Biol, 10, 411-417.  
14592866 S.Fuchs, R.Kasher, M.Balass, T.Scherf, M.Harel, M.Fridkin, J.L.Sussman, and E.Katchalski-Katzir (2003).
The binding site of acetylcholine receptor: from synthetic peptides to solution and crystal structure.
  Ann N Y Acad Sci, 998, 93.  
12727867 T.Grutter, L.Prado de Carvalho, N.Le Novère, P.J.Corringer, S.Edelstein, and J.P.Changeux (2003).
An H-bond between two residues from different loops of the acetylcholine binding site contributes to the activation mechanism of nicotinic receptors.
  EMBO J, 22, 1990-2003.  
12695308 T.K.Sixma, and A.B.Smit (2003).
Acetylcholine binding protein (AChBP): a secreted glial protein that provides a high-resolution model for the extracellular domain of pentameric ligand-gated ion channels.
  Annu Rev Biophys Biomol Struct, 32, 311-334.  
13679581 Y.Paas, J.Cartaud, M.Recouvreur, R.Grailhe, V.Dufresne, E.Pebay-Peyroula, E.M.Landau, and J.P.Changeux (2003).
Electron microscopic evidence for nucleation and growth of 3D acetylcholine receptor microcrystals in structured lipid-detergent matrices.
  Proc Natl Acad Sci U S A, 100, 11309-11314.  
12160749 A.Samson, T.Scherf, M.Eisenstein, J.Chill, and J.Anglister (2002).
The mechanism for acetylcholine receptor inhibition by alpha-neurotoxins and species-specific resistance to alpha-bungarotoxin revealed by NMR.
  Neuron, 35, 319-332.
PDB codes: 1l4w 1ljz 1lk1
11867717 C.Fruchart-Gaillard, B.Gilquin, S.Antil-Delbeke, N.Le Novère, T.Tamiya, P.J.Corringer, J.P.Changeux, A.Ménez, and D.Servent (2002).
Experimentally based model of a complex between a snake toxin and the alpha 7 nicotinic receptor.
  Proc Natl Acad Sci U S A, 99, 3216-3221.  
12006581 F.Teixeira-Clerc, A.Ménez, and P.Kessler (2002).
How do short neurotoxins bind to a muscular-type nicotinic acetylcholine receptor?
  J Biol Chem, 277, 25741-25747.  
12133834 H.Zeng, and E.Hawrot (2002).
NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica.
  J Biol Chem, 277, 37439-37445.
PDB codes: 1lxg 1lxh
12436428 J.Lindstrom (2002).
Autoimmune diseases involving nicotinic receptors.
  J Neurobiol, 53, 656-665.  
12162733 L.Bracci, L.Lozzi, A.Pini, B.Lelli, C.Falciani, N.Niccolai, A.Bernini, A.Spreafico, P.Soldani, and P.Neri (2002).
A branched peptide mimotope of the nicotinic receptor binding site is a potent synthetic antidote against the snake neurotoxin alpha-bungarotoxin.
  Biochemistry, 41, 10194-10199.  
11790782 L.Moise, A.Piserchio, V.J.Basus, and E.Hawrot (2002).
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, 277, 12406-12417.
PDB codes: 1kc4 1kfh 1kl8
11867716 N.Le Novère, T.Grutter, and J.P.Changeux (2002).
Models of the extracellular domain of the nicotinic receptors and of agonist- and Ca2+-binding sites.
  Proc Natl Acad Sci U S A, 99, 3210-3215.
PDB codes: 1ol3 1ol4 1ol8 1ol9 1ole 1olf 1olj 1olk
11988468 R.H.Spencer, and D.C.Rees (2002).
The alpha-helix and the organization and gating of channels.
  Annu Rev Biophys Biomol Struct, 31, 207-233.  
11683986 A.Karlin (2001).
Of snakes, snails, and surrogates.
  Neuron, 32, 173-174.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

spacer
spacer