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.

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

BERTOLANI, ARIANNA;PIZZI, ANDREA;PIRRIE, LISA;GAZZERA, LARA;CAVALLO, GABRIELLA;TERRANEO, GIANCARLO;METRANGOLO, PIERANGELO
2017-01-01

Abstract

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.
2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11311/1013011
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