TY - JOUR
T1 - Towards the role of metal ions in the structural variability of proteins
T2 - CdII speciation of a metal ion binding loop motif
AU - Jancsó, Attila
AU - Szunyogh, Dániel
AU - Larsen, Flemming Hofmann
AU - Thulstrup, Peter Waaben
AU - Christensen, Niels Johan
AU - Gyurcsik, Béla
AU - Hemmingsen, Lars Bo Stegeager
PY - 2011/12
Y1 - 2011/12
N2 - A de novo designed dodecapeptide (HS), inspired by the metal binding loops of metal-responsive transcriptional activators, was synthesized. The aim was to create a model system for structurally promiscuous and intrinsically unstructured proteins, and explore the effect of metal ions on their structure and dynamics. The interaction with Cd II was investigated by UV, synchrotron radiation CD, 1H NMR, and perturbed angular correlation (PAC) of γ-rays spectroscopy, pH-potentiometry, and molecular modelling. The peptide mainly displays characteristics of random coil in the CD spectra, and the molecular dynamics simulations demonstrate that it is unstructured with transient and varying helical content. The spectroscopic studies revealed the formation of loop structures with the coordination of the two Cys-thiolates close to each end of the HS peptide, in the presence of one equivalent of Cd II per ligand. The imidazole moiety from histidine is also bound to Cd II at neutral pH and above. In the presence of 0.5 equivalent of Cd II per HS metal bridged structures with e.g. CdS 2N 2 and possibly CdS 4 coordination geometries are formed above pH ∼6. In an equilibrium of several co-existing species the peptide is exchanging between a number of structures also in its metal ion bound state(s), as indicated by NMR and PAC data.
AB - A de novo designed dodecapeptide (HS), inspired by the metal binding loops of metal-responsive transcriptional activators, was synthesized. The aim was to create a model system for structurally promiscuous and intrinsically unstructured proteins, and explore the effect of metal ions on their structure and dynamics. The interaction with Cd II was investigated by UV, synchrotron radiation CD, 1H NMR, and perturbed angular correlation (PAC) of γ-rays spectroscopy, pH-potentiometry, and molecular modelling. The peptide mainly displays characteristics of random coil in the CD spectra, and the molecular dynamics simulations demonstrate that it is unstructured with transient and varying helical content. The spectroscopic studies revealed the formation of loop structures with the coordination of the two Cys-thiolates close to each end of the HS peptide, in the presence of one equivalent of Cd II per ligand. The imidazole moiety from histidine is also bound to Cd II at neutral pH and above. In the presence of 0.5 equivalent of Cd II per HS metal bridged structures with e.g. CdS 2N 2 and possibly CdS 4 coordination geometries are formed above pH ∼6. In an equilibrium of several co-existing species the peptide is exchanging between a number of structures also in its metal ion bound state(s), as indicated by NMR and PAC data.
U2 - 10.1039/c1mt00138h
DO - 10.1039/c1mt00138h
M3 - Journal article
C2 - 22041892
SN - 1756-5901
VL - 3
SP - 1331
EP - 1339
JO - Metallomics
JF - Metallomics
IS - 12
ER -