In this work a metal ion binding model dodecapeptide was investigated in terms of its capacity to adopt different structures depending on the metal ion to peptide stoichiometry. The dodecapeptide is much simpler than real proteins, yet displays sufficient complexity to model the effect of metal ions on fully or partially unstructured proteins, or the effect of metal ions on protein aggregation.
Metal ions may be employed to fold (or misfold) individual peptides in a controlled manner depending on the potential metal ion coordinating amino acid side chains (Cys, His, Asp, Glu, …) in the peptide, and the ligand and structural preferences of the metal ion (in our studies Zn2+, Cd2+, Hg2+, Cu+/2+). Simultaneously, new species such as metal ion bridged ternary complexes or even oligomers may be formed.
In recent previous studies we have observed similar polymorphism of zinc finger model peptides and amyloid-beta peptides [1,2], indicating that at least some metal ion binding proteins may exist in several structures, dictated by metal ion to peptide stoichiometry. I.e. these systems may exist in intermediate states different from the two extremes, the metal free and the fully metal ion loaded species.
[1] Heinz U., Hemmingsen L., Kiefer M., Adolph H.W. Structural Adaptability of Zinc Binding Sites: Different Structures in Partially, Fully, and Heavy Metal Loaded States Chem. Eur. J. 2009, 15, 7350-7358
[2] Pedersen J.T., Teilum K., Heegaard N.H.H, Østergaard J., Adolph H.W., Hemmingsen L. Cu(II) Binding to Amyloid-beta Peptides on the Millisecond Time-Scale Involves Formation of a Peptide-Metal-Peptide Complex and Precedes Oligomerization Angew. Chem. Int. Ed. 2011, 50, 2532-2535