Department of Biochemistry and Biophysics , Texas A&M University , 300 Olsen Boulevard , College Station , Texas 77843 , United States.
Department of Biology , Texas A&M University , College Station , Texas 77843 , United States.
Biochemistry. 2019 Feb 12;58(6):509-513. doi: 10.1021/acs.biochem.8b01235. Epub 2018 Dec 28.
Cd and Pb 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 Cd and Pb 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 Ca-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.
Cd 和 Pb 是异源重金属离子，它们通过离子模拟干扰生物大分子的细胞功能。我们采用 SAXS、电子显微镜、FRET 和溶液 NMR 光谱学的组合方法，证明 Cd 和 Pb 的处理会导致蛋白激酶 C 调节域的自组装，这些调节域与膜的外周相关联。自组装过程成功地与离子模拟竞争，并由与蛋白激酶 C 的典型 Ca 结合基序不同的保守蛋白区域介导。与单体相比，蛋白质寡聚体与阴离子膜相互作用的能力增强。我们的研究结果表明，金属离子依赖性的外周膜域可用于生成蛋白-金属离子纳米簇，并作为设计螯合剂的生物模板。
