Cd(II)- and Pb(II)-Induced Self-Assembly of Peripheral Membrane Domains from Protein Kinase C.
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Cd2+ and Pb2+ are xenobiotic heavy metal ions that use ionic mimicry to interfere with the cellular function of biomacromolecules. Using a combination of SAXS, electron microscopy, FRET, and solution NMR spectroscopy, we demonstrate that treatment with Cd2+ and Pb2+ causes self-assembly of protein kinase C regulatory domains that peripherally associate with membranes. The self-assembly process successfully competes with ionic mimicry and is mediated by conserved protein regions that are distinct from the canonical Ca2+-binding motifs of protein kinase C. The ability of protein oligomers to interact with anionic membranes is enhanced compared to the monomeric species. Our findings suggest that metal-ion-dependent peripheral membrane domains can be utilized for generating protein-metal-ion nanoclusters and serve as biotemplates for the design of sequestration agents.
author list (cited authors)
Cole, T. R., Erickson, S. G., Morales, K. A., Sung, M., Holzenburg, A., & Igumenova, T. I.
complete list of authors
Cole, Taylor R||Erickson, Samuel G||Morales, Krystal A||Sung, MinWoo||Holzenburg, Andreas||Igumenova, Tatyana I