1idl
From Proteopedia
THE NMR SOLUTION STRUCTURE OF ALPHA-BUNGAROTOXIN
Structural highlights
Function3L21A_BUNMU Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). It also shows an activity on GABA(A) receptors (PubMed:16549768, PubMed:25634239). It antagonises GABA-activated currents with high potency when tested on primary hippocampal neurons (PubMed:25634239). It inhibits recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3% inhibition at 20 uM of toxin) (PubMed:25634239). It also shows a weaker inhibition on GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2-GABRG2) subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:25634239). A very weak inhibition is also observed on GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) (PubMed:26221036). It has also been shown to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit (Kd=about 50 nM) (PubMed:16549768). In addition, it blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM) (PubMed:9840221).[1] [2] [3] [4] 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 PubMedThe region encompassing residues 181-98 on the alpha1 subunit of the muscle-type nicotinic acetylcholine receptor forms a major determinant for the binding of alpha-neurotoxins. We have prepared an (15)N-enriched 18-amino acid peptide corresponding to the sequence in this region to facilitate structural elucidation by multidimensional NMR. Our aim was to determine the structural basis for the high affinity, stoichiometric complex formed between this cognate peptide and alpha-bungarotoxin, a long alpha-neurotoxin. Resonances in the complex were assigned through heteronuclear and homonuclear NMR experiments, and the resulting interproton distance constraints were used to generate ensemble structures of the complex. Thr(8), Pro(10), Lys(38), Val(39), Val(40), and Pro(69) in alpha-bungarotoxin and Tyr(189), Tyr(190), Thr(191), Cys(192), Asp(195), and Thr(196) in the peptide participate in major intermolecular contacts. A comparison of the free and bound alpha-bungarotoxin structures reveals significant conformational rearrangements in flexible regions of alpha-bungarotoxin, mainly loops I, II, and the C-terminal tail. Furthermore, several of the calculated structures suggest that cation-pi interactions may be involved in binding. The root mean square deviation of the polypeptide backbone in the complex is 2.07 A. This structure provides, to date, the highest resolution description of the contacts between a prototypic alpha-neurotoxin and its cognate recognition sequence. 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.,Zeng H, Moise L, Grant MA, Hawrot E J Biol Chem. 2001 Jun 22;276(25):22930-40. Epub 2001 Apr 18. PMID:11312275[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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