铜（II）与 SARS-CoV-2 毒力因子 Nsp1 的无规则 C 末端肽结合。
Copper(II) Binding to the Intrinsically Disordered C-Terminal Peptide of SARS-CoV-2 Virulence Factor Nsp1.
机构信息
Beckman Institute, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, United States.
出版信息
Inorg Chem. 2022 Jun 20;61(24):8992-8996. doi: 10.1021/acs.inorgchem.2c01329. Epub 2022 Jun 5.
Abstract
The first encoded SARS-CoV-2 protein (Nsp1) binds to the human 40S ribosome and blocks synthesis of host proteins, thereby inhibiting critical elements of the innate immune response. The final 33 residues of the natively unstructured Nsp1 C-terminus adopt a helix-turn-helix geometry upon binding to the ribosome. We have characterized the fluctuating conformations of this peptide using circular dichroism spectroscopy along with measurements of tryptophan fluorescence and energy transfer. Tryptophan fluorescence decay kinetics reveal that copper(II) binds to the peptide at micromolar concentrations, and electron paramagnetic resonance spectroscopy indicates that the metal ion coordinates to the lone histidine residue.
摘要
第一个被编码的 SARS-CoV-2 蛋白（Nsp1）与人类 40S 核糖体结合，并阻止宿主蛋白的合成，从而抑制先天免疫反应的关键因素。在与核糖体结合后，天然无结构的 Nsp1 C 端的最后 33 个残基采用螺旋-转角-螺旋几何形状。我们使用圆二色性光谱以及色氨酸荧光和能量转移测量，对该肽的波动构象进行了表征。色氨酸荧光衰减动力学表明，铜（II）在微摩尔浓度下与肽结合，电子顺磁共振波谱表明金属离子与孤组氨酸残基配位。
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