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

Arianna Bertolani, Andrea Pizzi, Lisa Pirrie, Lara Gazzera, Giulia Morra, Massimiliano Meli, Giorgio Colombo, Alessandro Genoni, Gabriella Cavallo, Giancarlo Terraneo, Pierangelo Metrangolo*

*Corresponding author for this work

Research output: Contribution to journalArticleProfessional

16 Citations (Scopus)
3 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2051-2058
JournalCHEMISTRY: A EUROPEAN JOURNAL
Volume23
Issue number9
Early online date2016
DOIs
Publication statusPublished - 10 Feb 2017
MoE publication typeD1 Article in a trade journal

Keywords

  • Amyloid beta-peptides
  • Aromatic interactions
  • Crystal structures
  • Iodination
  • Peptides

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