Crystal Structure of the DFNKF Segment of Human Calcitonin Unveils Aromatic Interactions between Phenylalanines.
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.
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.
Arianna
A
Bertolani
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.
Andrea
A
Pizzi
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.
Lisa
L
Pirrie
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.
Lara
L
Gazzera
Istituto di Chimica del Riconoscimento Molecolare, CNR, Via Mario Bianco 9, 20131, Milano, Italy.
Giulia
G
Morra
Istituto di Chimica del Riconoscimento Molecolare, CNR, Via Mario Bianco 9, 20131, Milano, Italy.
Massimiliano
M
Meli
Istituto di Chimica del Riconoscimento Molecolare, CNR, Via Mario Bianco 9, 20131, Milano, Italy.
Giorgio
G
Colombo
Laboratoire SRSMC, UMR 7565, CNRS, Vandoeuvre-lès-Nancy, 54506, France.|Laboratoire SRSMC, UMR 7565, Université de Lorraine, Vandoeuvre-lès-Nancy, 54506, France.
Alessandro
A
Genoni
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.
Gabriella
G
Cavallo
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.
Giancarlo
G
Terraneo
Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via L. Mancinelli 7, 20131, Milano, Italy.|Istituto di Chimica del Riconoscimento Molecolare, CNR, Via Mario Bianco 9, 20131, Milano, Italy.|HYBER Centre of Excellence, Department of Applied Physics, Aalto University, P.O. Box 15100, 02150, Espoo, Finland.
Pierangelo
http://orcid.org/0000-0002-7945-099X
P
Metrangolo
D000595:Amino Acid Sequence; D002116:Calcitonin / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D056004:Molecular Dynamics Simulation; D010649:Phenylalanine / Q000737:chemistry*; D017433:Protein Structure, Secondary
D010649:Phenylalanine; D002116:Calcitonin
amyloid beta-peptides; aromatic interactions; crystal structures; iodination; peptides