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

Research output: Contribution to journalArticleProfessional

Researchers

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

Research units

  • Polytechnic University of Milan
  • Istituto di Chimica del Riconoscimento Molecolare
  • Université de Lorraine

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.

Details

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

    Research areas

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

ID: 10383332