1CMR

NMR SOLUTION STRUCTURE OF A CHIMERIC PROTEIN, DESIGNED BY TRANSFERRING A FUNCTIONAL SNAKE BETA-HAIRPIN INTO A SCORPION ALPHA/BETA SCAFFOLD (PH 3.5, 20C), NMR, 18 STRUCTURES

Summary for 1CMR

• Entry DOI: 10.2210/pdb1cmr/pdb
• Descriptor: CHARYBDOTOXIN, ALPHA CHIMERA (1 entity in total)
• Functional Keywords: antagonist of nicotinic acetylcholine receptor, curaremimetic protein
• Cellular location: Secreted : P13487
• Total number of polymer chains: 1
• Total formula weight: 3565.05

Authors

Zinn-Justin, S.,Guenneugues, M.,Drakopoulou, E.,Gilquin, B.,Vita, C.,Menez, A. (deposition date: 1996-03-15, release date: 1996-08-01, Last modification date: 2024-11-20)

Primary citation

Zinn-Justin, S.,Guenneugues, M.,Drakopoulou, E.,Gilquin, B.,Vita, C.,Menez, A.
Transfer of a beta-hairpin from the functional site of snake curaremimetic toxins to the alpha/beta scaffold of scorpion toxins: three-dimensional solution structure of the chimeric protein.
Biochemistry, 35:8535-8543, 1996

PubMed Abstract: The alpha/beta scorpion fold is shared by scorpion toxins, insect defensins, and plant thionins. This small and functionally versatile template contains an alpha-helix and a triple beta-sheet linked by three disulfide bridges. With the view to introduce novel functional centers within this fold, we replaced the sequence (the cysteines and glycines excepted) of the original beta-hairpin of a scorpion toxin by the sequence of a beta-hairpin that forms part of the site by which snake neurotoxins bind to nicotinic acetylcholine receptors (AcChOR). The resulting chimeric protein, synthesized by chemical means, binds to AcChOR, though with a lower affinity than the snake toxins [Drakopoulou; E., Zinn-Justin, S., Guenneugues, M., Gilquin, B., Ménez, A., & Vita, C. (1996) J. Biol. Chem. 271, 11979-11987]. The work described in this paper is an attempt to clarify the structural consequences associated with the transfer of the beta-hairpin. We report the determination of the three-dimensional solution structure of the chimeric protein by proton NMR spectroscopy and molecular dynamics calculations. Comparison of the structure of the chimera with those of the scorpion alpha/beta toxin and of the snake neurotoxin shows that (i) the new protein folds as an alpha/beta motif and (ii) the beta-hairpins of the chimera and of the curaremimetic toxin adopt a similar conformation. A closer inspection of the differences between the structures of the original and transferred beta-hairpins allows rationalization of the biological properties of the chimera.

PubMed: 8679614
DOI: 10.1021/bi960466n

Experimental method

SOLUTION NMR