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1kl8

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Revision as of 14:42, 27 October 2021

NMR STRUCTURAL ANALYSIS OF THE COMPLEX FORMED BETWEEN ALPHA-BUNGAROTOXIN AND THE PRINCIPAL ALPHA-NEUROTOXIN BINDING SEQUENCE ON THE ALPHA7 SUBUNIT OF A NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR

Structural highlights

1kl8 is a 2 chain structure with sequence from Bungarus multicinctus and Chick. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	1abt, 1idh, 2abx, 1i9b, 1hc9, 1jbd, 1kc4, 1kfh, 1haj, 1bxp, 1ikc
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NXL1A_BUNMU] Binds with high affinity to muscular and neuronal (alpha-7, alpha-8, and alpha-9) nicotinic acetylcholine receptors. Produces peripheral paralysis by blocking neuromuscular transmission at the postsynaptic site. Blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM).^[1] ^[2] [ACHA7_CHICK] After binding acetylcholine, 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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We report a new, higher resolution NMR structure of alpha-bungarotoxin that defines the structure-determining disulfide core and beta-sheet regions. We further report the NMR structure of the stoichiometric complex formed between alpha-bungarotoxin and a recombinantly expressed 19-mer peptide ((178)IPGKRTESFYECCKEPYPD(196)) derived from the alpha7 subunit of the chick neuronal nicotinic acetylcholine receptor. A comparison of these two structures reveals binding-induced stabilization of the flexible tip of finger II in alpha-bungarotoxin. The conformational rearrangements in the toxin create an extensive binding surface involving both sides of the alpha7 19-mer hairpin-like structure. At the contact zone, Ala(7), Ser(9), and Ile(11) in finger I and Arg(36), Lys(38), Val(39), and Val(40) in finger II of alpha-bungarotoxin interface with Phe(186), Tyr(187), Glu(188), and Tyr(194) in the alpha7 19-mer underscoring the importance of receptor aromatic residues as critical neurotoxin-binding determinants. Superimposing the structure of the complex onto that of the acetylcholine-binding protein (1I9B), a soluble homologue of the extracellular domain of the alpha7 receptor, places alpha-bungarotoxin at the peripheral surface of the inter-subunit interface occluding the agonist-binding site. The disulfide-rich core of alpha-bungarotoxin is suggested to be tilted in the direction of the membrane surface with finger II extending into the proposed ligand-binding cavity.

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.,Moise L, Piserchio A, Basus VJ, Hawrot E J Biol Chem. 2002 Apr 5;277(14):12406-17. Epub 2002 Jan 14. PMID:11790782^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Servent D, Winckler-Dietrich V, Hu HY, Kessler P, Drevet P, Bertrand D, Menez A. 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. PMID:9305882
↑ Dajas-Bailador F, Costa G, Dajas F, Emmett S. 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. PMID:9840221
↑ Moise L, Piserchio A, Basus VJ, Hawrot E. 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. Epub 2002 Jan 14. PMID:11790782 doi:10.1074/jbc.M110320200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1kl8"

@@ Line 3: / Line 3: @@
 <StructureSection load='1kl8' size='340' side='right'caption='[[1kl8]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1kl8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bunmu Bunmu] and [https://en.wikipedia.org/wiki/Chick Chick]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KL8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1kl8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [https://en.wikipedia.org/wiki/Chick Chick]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KL8 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1abt|1abt]], [[1idh|1idh]], [[2abx|2abx]], [[1i9b|1i9b]], [[1hc9|1hc9]], [[1jbd|1jbd]], [[1kc4|1kc4]], [[1kfh|1kfh]], [[1haj|1haj]], [[1bxp|1bxp]], [[1ikc|1ikc]]</div></td></tr>
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Bunmu]]
+[[Category: Bungarus multicinctus]]
 [[Category: Chick]]
 [[Category: Large Structures]]

1kl8

From Proteopedia

Revision as of 14:42, 27 October 2021

NMR STRUCTURAL ANALYSIS OF THE COMPLEX FORMED BETWEEN ALPHA-BUNGAROTOXIN AND THE PRINCIPAL ALPHA-NEUROTOXIN BINDING SEQUENCE ON THE ALPHA7 SUBUNIT OF A NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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