School of Basic Sciences, Indian Institute of Technology Mandi, VPO Kamand, Himachal Pradesh, 175005, India.
Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Virology. 2022 Jan;566:42-55. doi: 10.1016/j.virol.2021.11.005. Epub 2021 Nov 27.
All available SARS-CoV-2 spike protein crystal and cryo-EM structures have shown missing electron densities for cytosolic C-terminal regions (CTR). Generally, the missing electron densities point towards the intrinsically disordered nature of the protein region (IDPR). This curiosity has led us to investigate the cytosolic CTR of the spike glycoprotein of SARS-CoV-2 in isolation. The spike CTR is supposed to be from 1235 to 1273 residues or 1242-1273 residues based on our used prediction. Therefore, we have demonstrated the structural conformation of cytosolic region and its dynamics through computer simulations up to microsecond timescale using OPLS and CHARMM forcefields. The simulations have revealed the unstructured conformation of cytosolic region. Further, we have validated our computational observations with circular dichroism (CD) spectroscopy-based experiments and found its signature spectra at 198 nm. We believe that our findings will surely help in understanding the structure-function relationship of the spike protein's cytosolic region.
所有现有的 SARS-CoV-2 刺突蛋白晶体和 cryo-EM 结构都显示细胞质 C 末端区域（CTR）存在电子密度缺失。通常，电子密度缺失指向蛋白质区域的固有无序性质（IDPR）。这种好奇心促使我们对 SARS-CoV-2 刺突糖蛋白的细胞质 CTR 进行单独研究。根据我们的预测，刺突 CTR 应该是从 1235 到 1273 个残基或 1242-1273 个残基。因此，我们使用 OPLS 和 CHARMM 力场通过计算机模拟在微秒时间尺度上展示了细胞质区域的结构构象及其动力学。模拟揭示了细胞质区域的无规构象。此外，我们还通过基于圆二色性（CD）光谱的实验验证了我们的计算观察结果，并在 198nm 处发现了其特征谱。我们相信我们的发现肯定有助于理解刺突蛋白细胞质区域的结构-功能关系。
