Cd(II)- and Pb(II)-Induced Self-Assembly of Peripheral Membrane Domains from Protein Kinase C. Academic Article

abstract

• 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.

authors

• Igumenova, Tatyana

published proceedings

• Biochemistry

author list (cited authors)

• Cole, T. R., Erickson, S. G., Morales, K. A., Sung, M., Holzenburg, A., & Igumenova, T. I.

citation count

• 1

complete list of authors

• Cole, Taylor R||Erickson, Samuel G||Morales, Krystal A||Sung, MinWoo||Holzenburg, Andreas||Igumenova, Tatyana I

publication date

• February 2019

publisher

• American Chemical Society (ACS)  Publisher

published in

• Biochemistry  Journal

keywords

• Cadmium
• Cell Membrane
• Humans
• Lead
• Nanocomposites
• Protein Conformation
• Protein Domains
• Protein Kinase C

PubMed Central ID

• 30584764

Digital Object Identifier (DOI)

• 10.1021/acs.biochem.8b01235

start page

• 509

end page

• 513

volume

• 58

issue

• 6

URL

• http://dx.doi.org/10.1021/acs.biochem.8b01235