Department of Molecular and Cell Biology, National Analytical Ultracentrifugation Facility, University of Connecticut, Storrs, CT 06269, USA.
Macromol Biosci. 2010 Jul 7;10(7):703-13. doi: 10.1002/mabi.201000069.
Protein kinase R (PKR) is a central component of the interferon antiviral defense pathway. Upon binding to dsRNA, PKR undergoes autophosphorylation reactions that activate the kinase, resulting in the inhibition of protein synthesis in virally-infected cells. We have used analytical ultracentrifugation and related biophysical methods to quantitatively characterize the stoichiometries, affinities, and free energy couplings that govern the assembly of the macromolecular complexes in the PKR activation pathway. These studies demonstrate that PKR dimerization play a key role in enzymatic activation and support a model where the role of dsRNA is to bring two or more PKR monomers in close proximity to enhance dimerization.
蛋白激酶 R (PKR) 是干扰素抗病毒防御途径的核心组成部分。在与 dsRNA 结合后，PKR 经历自身磷酸化反应，激活激酶，导致病毒感染细胞中蛋白质合成的抑制。我们已经使用分析超速离心和相关的生物物理方法来定量表征控制 PKR 激活途径中大分子复合物组装的化学计量、亲和力和自由能偶联。这些研究表明，PKR 二聚化在酶激活中起着关键作用，并支持这样一种模型，即 dsRNA 的作用是将两个或更多 PKR 单体紧密靠近以增强二聚化。
