Towards understanding secondary structure transitions: phosphorylation and metal coordination in model peptides.
Secondary structure transitions are important modulators of signal transduction and protein aggregation. Phosphorylation is a well known post-translational modification capable of dramatic alteration of protein secondary structure. Additionally, phosphorylated residues can induce structural changes through metal binding. Data derived from the Protein Data Bank demonstrate that magnesium and manganese are metal ions most favored by phosphate. Due to the complexity of molecular interactions as well as the challenging physicochemical properties of natural systems, simplified peptide models have emerged as a useful tool for investigating the molecular switching phenomenon. In this study using a coiled coil model peptide, we show structural consequences of phosphorylation and subsequent magnesium and manganese ions coordination. In the course of our experiment we obtained a switch cascade starting from a stable helical conformation of the control peptide, continuing through the phosphorylation-induced unfolded structure, and ending with a metal-stabilized alpha-helix (Mg(2+)) or helical fibers (Mn(2+)), each of which could be transferred back to the unfolded form upon EDTA chelation. This study demonstrates how small peptide models can aid in the evaluation and a better understanding of protein secondary structure transitions.
Broncel
Malgorzata
M
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
Wagner
Sara C
SC
Paul
Kerstin
K
Hackenberger
Christian P R
CP
Koksch
Beate
B
D000595:Amino Acid Sequence; D002614:Chelating Agents / Q000737:chemistry; D002942:Circular Dichroism; D008274:Magnesium / Q000737:chemistry*; D008345:Manganese / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010766:Phosphorylation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D002614:Chelating Agents; D010455:Peptides; D008345:Manganese; D008274:Magnesium