School of Medicine Publications and Presentations

Document Type

Article

Publication Date

2-12-2019

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.

Comments

Copyright notice

Publication Title

Biochemistry

DOI

10.1021/acs.biochem.8b01235

Academic Level

faculty

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