Picosecond to Hour Time Scale Dynamics of a "Three Finger" Toxin: Correlation with Its Toxic and Antigenic Properties
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- 作者：Marc Guenneugues ; Pascal Drevet ; Suzanne Pinkasfeld ; Bernard Gilquin ; André ; Mé ; nez ; and Sophie Zinn-Justin
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：December 23, 1997
- 年：1997
- 卷：36
- 期：51
- 页码：16097 - 16108
- 全文大小：277K
- 年卷期：v.36,no.51(December 23, 1997)
- ISSN：1520-4995
文摘
Toxin 
from Naja nigricollis (61 aminoacids, four disulfide bridges) belongs to the "threefinger" fold family, which contains snake toxins with variousbiological activities and nontoxic proteinsfrom different origins. In this paper, we report an extensive1H and 15N NMR study of the dynamicsoftoxin in solution. 15N relaxation, 1Hoff-resonance ROESY, and H-D exchange experimentsallowedus to probe picosecond to hour motions in the protein. Analysis ofthese NMR measurements demonstratesthat toxin exhibits various time scale motions, i.e., particularlylarge amplitude picosecond to nanosecondmotions at the tips of the loops, observable microsecond to millisecondmotions around two disulfidebridges, second time scale motions around the C-N bonds of asparagineand glutamine side chains whichare more or less rapid depending on their amino acid solventaccessibility, and minute to hour motionsin the 
-sheet structure. The less well-defined regions of toxin solution structures are subject to importantpicosecond to nanosecond motions. The toxic site is organizedaround residues belonging to the rigidcore of the molecule but also comprises residues exhibiting dynamics onvarious time scales. The M1epitope is subject to large picosecond to millisecond motions, whichare probably modified by the interactionwith the antibody. This phenomenon could be linked to theneutralizing properties of the antibody.
from Naja nigricollis (61 aminoacids, four disulfide bridges) belongs to the "threefinger" fold family, which contains snake toxins with variousbiological activities and nontoxic proteinsfrom different origins. In this paper, we report an extensive1H and 15N NMR study of the dynamicsoftoxin in solution. 15N relaxation, 1Hoff-resonance ROESY, and H-D exchange experimentsallowedus to probe picosecond to hour motions in the protein. Analysis ofthese NMR measurements demonstratesthat toxin exhibits various time scale motions, i.e., particularlylarge amplitude picosecond to nanosecondmotions at the tips of the loops, observable microsecond to millisecondmotions around two disulfidebridges, second time scale motions around the C-N bonds of asparagineand glutamine side chains whichare more or less rapid depending on their amino acid solventaccessibility, and minute to hour motionsin the -sheet structure. The less well-defined regions of toxin solution structures are subject to importantpicosecond to nanosecond motions. The toxic site is organizedaround residues belonging to the rigidcore of the molecule but also comprises residues exhibiting dynamics onvarious time scales. The M1epitope is subject to large picosecond to millisecond motions, whichare probably modified by the interactionwith the antibody. This phenomenon could be linked to theneutralizing properties of the antibody.