Zhang Rongfu, Qin Huajun, Prasad Ramesh, Fu Riqiang, Zhou Huan-Xiang, Cross Timothy A
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306.
National High Magnetic Field Laboratory, Tallahassee, FL 32310.
bioRxiv. 2023 May 8:2023.05.07.539752. doi: 10.1101/2023.05.07.539752.
The SARS-CoV-2 E protein is a transmembrane (TM) protein with its N-terminus exposed on the external surface of the virus. Here, the TM structure of the E protein is characterized by oriented sample and magic angle spinning solid-state NMR in lipid bilayers and refined by molecular dynamics simulations. This protein has been found to be a pentamer, with a hydrophobic pore that appears to function as an ion channel. We identified only a symmetric helix-helix interface, leading to a dimeric structure that does not support channel activity. The two helices have a tilt angle of only 6°, resulting in an extended interface dominated by Leu and Val sidechains. While residues Val14-Thr35 are almost all buried in the hydrophobic region of the membrane, Asn15 lines a water-filled pocket that potentially serves as a drug-binding site. The E and other viral proteins may adopt different oligomeric states to help perform multiple functions.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的E蛋白是一种跨膜（TM）蛋白，其N端暴露于病毒外表面。在此，通过在脂质双层中进行定向样品和魔角旋转固态核磁共振对E蛋白的跨膜结构进行了表征，并通过分子动力学模拟进行了优化。已发现该蛋白为五聚体，具有一个似乎起离子通道作用的疏水孔。我们仅鉴定出一个对称的螺旋-螺旋界面，导致形成不支持通道活性的二聚体结构。这两个螺旋的倾斜角仅为6°，形成了一个由亮氨酸和缬氨酸侧链主导的延伸界面。虽然缬氨酸14-苏氨酸35残基几乎全部埋在膜的疏水区域中，但天冬酰胺15排列在一个可能用作药物结合位点的充满水的口袋中。E蛋白和其他病毒蛋白可能采用不同的寡聚状态来帮助执行多种功能。
