Cited by 40Protein Structure and DynamicsChemical Synthesis and AnalysisLipid Membrane Structure and Behavior

Solution Structure, Dimerization, and Dynamics of a Lipophilic α/310-Helical, Cα-Methylated Peptide. Implications for Folding of Membrane Proteins

Dehner, Alexander, Planker, Eckart, Gemmecker, Gerd, Broxterman, Quirinus B., Bisson, William, Formaggio, Fernando, Crisma, Marco, Toniolo, Claudio +1 more·2001·Journal of the American Chemical Society

Abstract

The solution structure and the dimerization behavior of the lipophilic, highly C(alpha)-methylated model peptide, mBrBz-Iva(1)-Val(2)-Iva(3)-(alphaMe)Val(4)-(alphaMe)Phe(5)-(alphaMe)Val(6)-Iva(7)-NHMe, was studied by NMR spectroscopy and molecular dynamics simulations. The conformational analysis resulted in a right-handed 3(10)/alpha-helical equilibrium fast on the NMR time scale with a slight preference for the alpha-helical conformation. The NOESY 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 these findings are consistent with an antiparallel side-by-side dimerization. The structure of the dimeric peptide was calculated with a simulated annealing strategy. The lipophilic dimer is held together by favorable van der Waals interactions in the sense of a bulge fitting into a groove. The flexibility of the helical conformations concerning an alpha/3(10)-helical equilibrium is shown in a 3 ns molecular dynamics simulation of the resulting dimeric structure. Both overall helical structures of each monomer and the antiparallel mode of dimerization are stable. However, transitions were seen of several residues from a 3(10)-helical into an alpha-helical conformation and vice versa. Hence, this peptide represents a good model in which two often-discussed aspects of hierarchical transmembrane protein folding are present: i <-- i + 3 and i <-- i + 4 local H-bonding interactions cause a specific molecular shape which is then recognized as attractive by other surrounding structures.

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Crossref · 10.1021/ja010635d

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Authors
Dehner, A., Planker, E., Gemmecker, G., Broxterman, Q. B., Bisson, W., Formaggio, F., Crisma, M., Toniolo, C., & Kessler, H.
Affiliations
University of Padua (IT)
Corresponding author
Kessler, Horst
Venue
Journal of the American Chemical Society
Published
2001-06-19
Volume
123
Issue
27
Pages
6678-6686
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
OpenAlex
W1980616161
Cited by
40
References
45
Citations by year
2024: 1 · 2014: 1 · 2013: 1 · 2012: 2
FWCI
1.98
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of the American Chemical Society (publishedVersion)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
310-helix, alpha-helix, peptide dimerization, antiparallel dimer, membrane protein folding, hydrodynamic radius, van der Waals interactions, hydrogen bonding, model peptides
MeSH terms
Membrane Lipids, Membrane Proteins, Methylation, Oligopeptides, Solutions, Thermodynamics, Protein Structure, Secondary, Protein Folding, Dimerization, Nuclear Magnetic Resonance, Biomolecular

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