Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata 700009, India.
J Phys Chem B. 2023 Aug 10;127(31):6940-6948. doi: 10.1021/acs.jpcb.3c02286. Epub 2023 Jul 31.
SARS-CoV-2 spike glycoprotein is anchored by gangliosides. The sialic acid in the ganglioside headgroup is responsible for virus attachment and entry into host cells. We used coarse-grained (CG) molecular dynamics simulations to expand on our previous study of GM1 interaction with two different orientations of the SARS-CoV-2 S1 subunit N-terminal domain (NTD) and to confirm the role of sialic acid receptors in driving the viral receptor; GM3 was used as another ganglioside on the membrane. Because of the smaller headgroup, sialic acid is crucial in GM3 interactions, whereas GM1 interacts with NTD via both the sialic acid and external galactose. In line with our previous findings for NTD orientations in GM1 binding, we identified two orientations, "compact" and "distributed", comprising sugar receptor-interacting residues in GM3-embedded lipid bilayers. Gangliosides in closer proximity to the compact NTD orientation might cause relatively greater restrictions to penetrate the bilayer. However, the attachment of a distributed NTD orientation with more negative interaction energies appears to facilitate GM1/GM3 to move quickly across the membrane. Our findings likely shed some light on the orientations that the NTD receptor acquires during the early phases of interaction with GM1 and GM3 in a membrane environment.
SARS-CoV-2 刺突糖蛋白通过神经节苷脂锚定。神经节苷脂头部的唾液酸负责病毒附着和进入宿主细胞。我们使用粗粒（CG）分子动力学模拟来扩展我们之前关于 GM1 与 SARS-CoV-2 S1 亚基 N 端结构域（NTD）两种不同取向相互作用的研究，并确认唾液酸受体在驱动病毒受体中的作用；GM3 被用作膜上的另一种神经节苷脂。由于头部较小，唾液酸在 GM3 相互作用中至关重要，而 GM1 通过唾液酸和外部半乳糖与 NTD 相互作用。与我们之前在 GM1 结合中 NTD 取向的发现一致，我们在 GM3 嵌入脂质双层中鉴定了两种取向，“紧凑”和“分散”，包含糖受体相互作用残基。与紧凑 NTD 取向更接近的神经节苷脂可能会对穿透双层造成相对较大的限制。然而，具有更多负相互作用能的分散 NTD 取向的附着似乎有利于 GM1/GM3 快速穿过膜。我们的研究结果可能阐明了 NTD 受体在与 GM1 和 GM3 在膜环境中相互作用的早期阶段获得的取向。
