Salmon Calcitonin and Amyloid β: Two Peptides with Amyloidogenic Capacity Adopt Different Conformational Manifolds in Their Unfolded States
| Autor: | Thomas J. Measey, Reinhard Schweitzer-Stenner, Fatma Eker, Kai Griebenow, Andrew Hagarman |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Calcitonin
Protein Folding Protein Conformation Stereochemistry Peptide Spectrum Analysis Raman Biochemistry Molecular mechanics symbols.namesake Spectroscopy Fourier Transform Infrared Humans Salmon calcitonin Amino Acids Polyproline helix chemistry.chemical_classification Amyloid beta-Peptides Aqueous solution Chemistry Circular Dichroism Crystallography Structural Homology Protein Vibrational circular dichroism symbols Thermodynamics Peptides Raman spectroscopy |
| Zdroj: | Biochemistry. 45:2810-2819 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi052282r |
| Popis: | The molecular conformations of salmon calcitonin in aqueous solution have been investigated by exploiting the different influences of excitonic coupling on the amide I band profile in the isotropic and anisotropic Raman, FTIR, and vibrational circular dichroism spectra of a polypeptide. The N-terminal loop, caused by a disulfide bridge between cysteines at positions 1 and 7, was modeled by performing a conformational search by molecular mechanics calculations. The remaining part of the peptide chain was modeled as a mixture of three sequences containing different fractions of residues adopting poly-l-proline II (PPII), extended beta-strand, and alpha-helix-like conformations. This yielded an excellent reproduction of the experimentally observed amide I' band profiles. A comparison with recent data on the beta-amyloid fragment Abeta(1)(-)(28) revealed a lower PPII content and more conformational heterogeneity for calcitonin. Thus, our results underscore the notion that individual structural propensities of amino acid residues give rise to structural differences between the unfolded states of even long peptide chains, at variance with expectations based on a random or statistical coil model. |
| Databáze: | OpenAIRE |
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