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Salmon calcitonin and amyloid beta: two peptides with amyloidogenic capacity adopt different conformational manifolds in their unfolded states
Journal article   Peer reviewed

Salmon calcitonin and amyloid beta: two peptides with amyloidogenic capacity adopt different conformational manifolds in their unfolded states

Reinhard Schweitzer-Stenner, Thomas Measey, Andrew Hagarman, Fatma Eker and Kai Griebenow
Biochemistry (Easton), v 45(9), pp 2810-2819
07 Mar 2006
PMID: 16503636

Abstract

Thermodynamics Peptides - chemistry Calcitonin - chemistry Humans Amino Acids - chemistry Protein Conformation Spectrum Analysis, Raman Structural Homology, Protein Amyloid beta-Peptides - chemistry Spectroscopy, Fourier Transform Infrared Circular Dichroism Protein Folding
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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