Structural Difference between Group I and Group II Cobra Cardiotoxins: X-ray, NMR, and CD Analysis of the Effect of cis-Proline Conformation on Three-Fingered Toxins
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- 作者：Ting-Shou Chen ; Fong-Yu Chung ; Siu-Cin Tjong ; King-Siang Goh ; Wei-Ning Huang ; Kun-Yi Chien ; Po-Long Wu ; Hua-Ching Lin ; Chun-Jung Chen ; and Wen-guey Wu
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：May 24, 2005
- 年：2005
- 卷：44
- 期：20
- 页码：7414 - 7426
- 全文大小：990K
- 年卷期：v.44,no.20(May 24, 2005)
- ISSN：1520-4995
文摘
Natural homologues of cobra cardiotoxins (CTXs) were classified into two structural subclassesof group I and II based on the amino acid sequence and circular dichroism analysis, but the exact differencesin their three-dimensional structures and biological significance remain elusive. We show by circulardichroism, NMR spectroscopic, and X-ray crystallographic analyses of a newly purified group I CTX A6from eastern Taiwan cobra (Naja atra) venoms that its loop I conformation adopts a type VIa turn witha cis peptide bond located between two proline residues of PPxY. A similar "banana-twisted" conformationcan be observed in other group I CTXs and also in cyclolinopeptide A and its analogues. By binding tothe membrane environment, group I CTX undergoes a conformational change to adopt a more extendedhydrophobic domain with 
-sheet twisting closer to the one adopted by group II CTX. This result resolvesa discrepancy in the CTX structural difference reported previously between solution as well as crystalstate and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an importantrole in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalizationare also discussed on the basis of the determined loop I conformation.
-sheet twisting closer to the one adopted by group II CTX. This result resolvesa discrepancy in the CTX structural difference reported previously between solution as well as crystalstate and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an importantrole in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalizationare also discussed on the basis of the determined loop I conformation.