1ug4

From Proteopedia

Revision as of 12:31, 20 March 2008

Crystal Structure of Cardiotoxin VI from Taiwan Cobra (Naja atra) Venom

Overview

Natural homologues of cobra cardiotoxins (CTXs) were classified into two structural subclasses of group I and II based on the amino acid sequence and circular dichroism analysis, but the exact differences in their three-dimensional structures and biological significance remain elusive. We show by circular dichroism, NMR spectroscopic, and X-ray crystallographic analyses of a newly purified group I CTX A6 from eastern Taiwan cobra (Naja atra) venoms that its loop I conformation adopts a type VIa turn with a cis peptide bond located between two proline residues of PPxY. A similar "banana-twisted" conformation can be observed in other group I CTXs and also in cyclolinopeptide A and its analogues. By binding to the membrane environment, group I CTX undergoes a conformational change to adopt a more extended hydrophobic domain with beta-sheet twisting closer to the one adopted by group II CTX. This result resolves a discrepancy in the CTX structural difference reported previously between solution as well as crystal state and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an important role in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalization are also discussed on the basis of the determined loop I conformation.

About this Structure

1UG4 is a Single protein structure of sequence from Naja atra. Full crystallographic information is available from OCA.

Reference

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., Chen TS, Chung FY, Tjong SC, Goh KS, Huang WN, Chien KY, Wu PL, Lin HC, Chen CJ, Wu WG, Biochemistry. 2005 May 24;44(20):7414-26. PMID:15895985

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