1IE6

SOLUTION STRUCTURE OF IMPERATOXIN A

1IE6 の概要

• エントリーDOI: 10.2210/pdb1ie6/pdb
• 分子名称: IMPERATOXIN A (1 entity in total)
• 機能のキーワード: triple stranded antiparellel beta-sheet, inhibitory cystine knot, toxin
• 細胞内の位置: Secreted: P59868
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3776.49

構造登録者

Lee, C.W.,Takeuchi, K.,Takahashi, H.,Sato, K.,Shimada, I.,Kim, D.H.,Kim, J.I. (登録日: 2001-04-07, 公開日: 2003-06-10, 最終更新日: 2024-10-09)

主引用文献

Lee, C.W.,Lee, E.H.,Takeuchi, K.,Takahashi, H.,Shimada, I.,Sato, K.,Shin, S.Y.,Kim, D.H.,Kim, J.I.
Molecular basis of the high-affinity activation of type 1 ryanodine receptors by imperatoxin A.
Biochem.J., 377:385-394, 2004

PubMed Abstract: 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.

PubMed: 14535845
DOI: 10.1042/BJ20031192

実験手法

SOLUTION NMR