Position-dependent effects of fluorinated amino acids on the hydrophobic core formation of a heterodimeric coiled coil.
Systematic model investigations of the molecular interactions of fluorinated amino acids within native protein environments substantially improve our understanding of the unique properties of these building blocks. A rationally designed heterodimeric coiled coil peptide (VPE/VPK) and nine variants containing amino acids with variable fluorine content in either position a16 or d19 within the hydrophobic core were synthesized and used to evaluate the impact of fluorinated amino acid substitutions within different hydrophobic protein microenvironments. The structural and thermodynamic stability of the dimers were examined by applying both experimental (CD spectroscopy, FRET, and analytical ultracentrifugation) and theoretical (MD simulations and MM-PBSA free energy calculations) methods. The coiled coil environment imposes position-dependent conformations onto the fluorinated side chains and thus affects their packing and relative orientation towards their native interaction partners. We find evidence that such packing effects exert a significant influence on the contribution of fluorine-induced polarity to coiled coil folding.
Salwiczek
Mario
M
Department of Biology, Chemistry, and Pharmacy, Freie Universiät Berlin, Institute of Chemistry and Biochemistry-Organic Chemistry, Takustrasse 3, 14195 Berlin, Germany.
Samsonov
Sergey
S
Vagt
Toni
T
Nyakatura
Elisabeth
E
Fleige
Emanuel
E
Numata
Jorge
J
Cölfen
Helmut
H
Pisabarro
M Teresa
MT
Koksch
Beate
B
D000596:Amino Acids / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D000596:Amino Acids; D006845:Hydrocarbons, Fluorinated; D011506:Proteins