1kfh: Difference between revisions
New page: left|200px<br /><applet load="1kfh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kfh" /> '''Solution Structure of alpha-Bungarotoxin by ... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1kfh.jpg|left|200px]]<br /><applet load="1kfh" size=" | [[Image:1kfh.jpg|left|200px]]<br /><applet load="1kfh" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1kfh" /> | caption="1kfh" /> | ||
'''Solution Structure of alpha-Bungarotoxin by NMR Spectroscopy'''<br /> | '''Solution Structure of alpha-Bungarotoxin by NMR Spectroscopy'''<br /> | ||
==Overview== | ==Overview== | ||
We report a new, higher resolution NMR structure of alpha-bungarotoxin | 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. | ||
==About this Structure== | ==About this Structure== | ||
1KFH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. Full crystallographic information is available from [http:// | 1KFH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KFH OCA]. | ||
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Bungarus multicinctus]] | [[Category: Bungarus multicinctus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Basus, V | [[Category: Basus, V J.]] | ||
[[Category: Hawrot, E.]] | [[Category: Hawrot, E.]] | ||
[[Category: Moise, L.]] | [[Category: Moise, L.]] | ||
| Line 20: | Line 20: | ||
[[Category: long snake neurotoxin]] | [[Category: long snake neurotoxin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:32 2008'' | ||
Revision as of 14:33, 21 February 2008
|
Solution Structure of alpha-Bungarotoxin by NMR Spectroscopy
OverviewOverview
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.
About this StructureAbout this Structure
1KFH is a Single protein structure of sequence from Bungarus multicinctus. Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Thu Feb 21 13:33:32 2008