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Crystal Structure of the DFNKF Segment of Human Calcitonin Unveils Aromatic Interactions between Phenylalanines

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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en

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Chemistry: A European Journal, Volume 23, issue 9, pp. 2051-2058

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Although intensively studied, the high-resolution crystal structure of the peptide DFNKF, the core-segment of human calcitonin, has never been described. Here we report how the use of iodination as a strategy to promote crystallisation and facilitate phase determination, allowed us to solve, for the first time, the single-crystal X-ray structure of a DFNKF derivative. Computational studies suggest that both the iodinated and the wild-type peptides populate very similar conformations. Furthermore, the conformer found in the solid-state structure is one of the most populated in solution, making the crystal structure a reliable model for the peptide in solution. The crystal structure of DFNKF(I) confirms the overall features of the amyloid cross-β spine and highlights how aromatic-aromatic interactions are important structural factors in the self-assembly of this peptide. A detailed analysis of such interactions is reported.

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Bertolani, A, Pizzi, A, Pirrie, L, Gazzera, L, Morra, G, Meli, M, Colombo, G, Genoni, A, Cavallo, G, Terraneo, G & Metrangolo, P 2017, 'Crystal Structure of the DFNKF Segment of Human Calcitonin Unveils Aromatic Interactions between Phenylalanines', Chemistry: A European Journal, vol. 23, no. 9, pp. 2051-2058. https://doi.org/10.1002/chem.201604639

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