一种来自紫色芋螺毒液的烟碱型乙酰胆碱受体的非竞争性肽抑制剂。

A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom.

作者信息

Shon K J, Grilley M, Jacobsen R, Cartier G E, Hopkins C, Gray W R, Watkins M, Hillyard D R, Rivier J, Torres J, Yoshikami D, Olivera B M

机构信息

Department of Biology and Pathology, University of Utah, Salt Lake City, Utah, 84112, USA.

出版信息

Biochemistry. 1997 Aug 5;36(31):9581-7. doi: 10.1021/bi970235w.

DOI:10.1021/bi970235w

PMID:9236004

Abstract

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).

摘要

一种麻痹性肽，ψ-芋螺毒素Piiie已从紫色芋螺毒液中纯化并鉴定。电生理研究表明，该肽抑制烟碱型乙酰胆碱受体（nAChR）。然而，该肽并不阻断竞争性nAChR拮抗剂α-银环蛇毒素的结合。因此，ψ-芋螺毒素Piiie似乎在乙酰胆碱结合位点以外的位点抑制该受体。通过序列分析、质谱分析和化学合成确定，该肽具有以下共价结构：HOOCCLYGKCRRYOGCSSASCCQR*（O = 4-反式羟脯氨酸；*表示C末端酰胺化）。该毒素的二硫键连接与α-或αA-芋螺毒素无关，α-或αA-芋螺毒素是nAChR的竞争性抑制剂的芋螺肽家族，但与μ-芋螺毒素（它们是Na+通道阻滞剂）具有同源性。