1ie6: Difference between revisions
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ie6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ie6 OCA], [http://www.ebi.ac.uk/pdbsum/1ie6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ie6 RCSB]</span> | |||
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[[Category: triple stranded antiparellel beta-sheet]] | [[Category: triple stranded antiparellel beta-sheet]] | ||
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Revision as of 21:18, 30 March 2008
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SOLUTION STRUCTURE OF IMPERATOXIN A
OverviewOverview
Both imperatoxin A (IpTx(a)), a 33-residue peptide toxin from scorpion venom, and peptide A, derived from the II-III loop of dihydropyridine receptor (DHPR), interact specifically with the skeletal ryanodine receptor (RyR1), which is a Ca(2+)-release channel in the sarcoplasmic reticulum, but with considerably different affinities. IpTx(a) activates RyR1 with nanomolar affinity, whereas peptide A activates RyR1 at micromolar concentrations. To investigate the molecular basis for high-affinity activation of RyR1 by IpTx(a), we have determined the NMR solution structure of IpTx(a), and identified its functional surface by using alanine-scanning analogues. A detailed comparison of the functional surface profiles for two peptide activators revealed that IpTx(a) exhibits a large functional surface area (approx. 1900 A(2), where 1 A=0.1 nm), based on a short double-stranded antiparallel beta-sheet structure, while peptide A bears a much smaller functional surface area (approx. 800 A(2)), with the five consecutive basic residues (Arg(681), Lys(682), Arg(683), Arg(684) and Lys(685)) being clustered at the C-terminal end of the alpha-helix. The functional surface of IpTx(a) is composed of six essential residues (Leu(7), Lys(22), Arg(23), Arg(24), Arg(31) and Arg(33)) and several other important residues (His(6), Lys(8), Arg(9), Lys(11), Lys(19), Lys(20), Gly(25), Thr(26), Asn(27) and Lys(30)), indicating that amino acid residues involved in RyR1 activation make up over the half of the toxin molecule with the exception of cysteine residues. Taken together, these results suggest that the site where peptide A binds to RyR1 belongs to a subset of macrosites capable of being occupied by IpTx(a), resulting in differing the affinity and the mode of activation.
About this StructureAbout this Structure
1IE6 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Molecular basis of the high-affinity activation of type 1 ryanodine receptors by imperatoxin A., Lee CW, Lee EH, Takeuchi K, Takahashi H, Shimada I, Sato K, Shin SY, Kim DH, Kim JI, Biochem J. 2004 Jan 15;377(Pt 2):385-94. PMID:14535845
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