Crystal Structure of the DFNKF Segment of Human Calcitonin Unveils Aromatic Interactions between Phenylalanines. Issue 9 (15th December 2016)

• Record Type: Journal Article
• Authors: Bertolani, Arianna; Pizzi, Andrea; Pirrie, Lisa; Gazzera, Lara; Morra, Giulia; Meli, Massimiliano; Colombo, Giorgio; Genoni, Alessandro; Cavallo, Gabriella; Terraneo, Giancarlo; Metrangolo, Pierangelo
• Is Part Of: Chemistry. Volume 23:Issue 9(2017)
• Page Start: 2051
• Page End: 2058
• Publication Date: 2016-12-15
• Subjects: amyloid beta-peptides -- aromatic interactions -- crystal structures -- iodination -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201604639
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Easy on the I : The DFNKF pentapeptide (see figure), an amyloidogenic segment derived from the hormone human calcitonin (hCT), is a well‐studied model for amyloid formation. Here it is shown how iodination as a strategy to promote crystallisation and facilitate phase determination, allowed the single‐crystal X‐ray structure of a DFNKF derivative to be solved. Computational studies suggest that both the iodinated and the wild‐type peptides populate very similar conformations.