HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gilquin, B. Articles by Ménez, A. Search for Related Content PubMed PubMed Citation Articles by Gilquin, B. Articles by Ménez, A. Social Bookmarking                   What's this?

Motions and structural variability within toxins: Implication for their use as scaffolds for protein engineering

Département d’Ingénierie et d’Etude des Protéines, CEA, 91191 Gif sur Yvette, France

Reprint requests to: Bernard Gilquin, Département d’Ingénierie et d’Etude des Protéines, CEA, CE Saclay, Bat 152, 91191 Gif sur Yvette, France; e-mail: bgilquin{at}cea.fr; fax: (33)1 69 08 90 71.

Animal toxins are small proteins built on the basis of a few disulfide bonded frameworks. Because of their high variability in sequence and biologic function, these proteins are now used as templates for protein engineering. Here we report the extensive characterization of the structure and dynamics of two toxin folds, the "three-finger" fold and the short /ß scorpion fold found in snake and scorpion venoms, respectively. These two folds have a very different architecture; the short /ß scorpion fold is highly compact, whereas the "three-finger" fold is a ß structure presenting large flexible loops. First, the crystal structure of the snake toxin was solved at 1.8-Å resolution. Then, long molecular dynamics simulations (10 ns) in water boxes of the snake toxin and the scorpion charybdotoxin were performed, starting either from the crystal or the solution structure. For both proteins, the crystal structure is stabilized by more hydrogen bonds than the solution structure, and the trajectory starting from the X-ray structure is more stable than the trajectory started from the NMR structure. The trajectories started from the X-ray structure are in agreement with the experimental NMR and X-ray data about the protein dynamics. Both proteins exhibit fast motions with an amplitude correlated to their secondary structure. In contrast, slower motions are essentially only observed in toxin . The regions submitted to rare motions during the simulations are those that exhibit millisecond time-scale motions. Lastly, the structural variations within each fold family are described. The localization and the amplitude of these variations suggest that the regions presenting large-scale motions should be those tolerant to large insertions or deletions.

Keywords: Toxin; scaffold; structure; dynamics; protein engineering

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?