Solution Structure, Dimerization, and Dynamics of a Lipophilic /310-Helical, C
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- 作者：Alexander Dehner ; Eckart Planker ; Gerd Gemmecker ; Quirinus B. Broxterman ; William Bisson ; Fernando Formaggio ; Marco Crisma ; Claudio Toniolo ; and Horst Kessler
- 刊名：Journal of the American Chemical Society
- 出版年：2001
- 出版时间：July 11, 2001
- 年：2001
- 卷：123
- 期：27
- 页码：6678 - 6686
- 全文大小：586K
- 年卷期：v.123,no.27(July 11, 2001)
- ISSN：1520-5126
文摘
The solution structure and the dimerization behavior of the lipophilic, highly C
-methylated modelpeptide, mBrBz-Iva1-Val2-Iva3-(Me)Val4-(Me)Phe5-(Me)Val6-Iva7-NHMe, was studied by NMR spectroscopy and molecular dynamics simulations. The conformational analysis resulted in a right-handed 310/-helical equilibrium fast on the NMR time scale with a slight preference for the -helical conformation. TheNOESY spectrum showed intermolecular NOEs due to an aggregation of the heptapeptide. In addition,temperature-dependent diffusion measurements were performed to calculate the hydrodynamic radius. All thesefindings are consistent with an antiparallel side-by-side dimerization. The structure of the dimeric peptide wascalculated with a simulated annealing strategy. The lipophilic dimer is held together by favorable van derWaals interactions in the sense of a bulge fitting into a groove. The flexibility of the helical conformationsconcerning an /310-helical equilibrium is shown in a 3 ns molecular dynamics simulation of the resultingdimeric structure. Both overall helical structures of each monomer and the antiparallel mode of dimerizationare stable. However, transitions were seen of several residues from a 310-helical into an -helical conformationand vice versa. Hence, this peptide represents a good model in which two often-discussed aspects of hierarchicaltransmembrane protein folding are present: i 
i + 3 and i i + 4 local H-bonding interactions cause aspecific molecular shape which is then recognized as attractive by other surrounding structures.
-methylated modelpeptide, mBrBz-Iva1-Val2-Iva3-(Me)Val4-(Me)Phe5-(Me)Val6-Iva7-NHMe, was studied by NMR spectroscopy and molecular dynamics simulations. The conformational analysis resulted in a right-handed 310/-helical equilibrium fast on the NMR time scale with a slight preference for the -helical conformation. TheNOESY spectrum showed intermolecular NOEs due to an aggregation of the heptapeptide. In addition,temperature-dependent diffusion measurements were performed to calculate the hydrodynamic radius. All thesefindings are consistent with an antiparallel side-by-side dimerization. The structure of the dimeric peptide wascalculated with a simulated annealing strategy. The lipophilic dimer is held together by favorable van derWaals interactions in the sense of a bulge fitting into a groove. The flexibility of the helical conformationsconcerning an /310-helical equilibrium is shown in a 3 ns molecular dynamics simulation of the resultingdimeric structure. Both overall helical structures of each monomer and the antiparallel mode of dimerizationare stable. However, transitions were seen of several residues from a 310-helical into an -helical conformationand vice versa. Hence, this peptide represents a good model in which two often-discussed aspects of hierarchicaltransmembrane protein folding are present: i i + 3 and i i + 4 local H-bonding interactions cause aspecific molecular shape which is then recognized as attractive by other surrounding structures.