Carlos Chagas Filho Biophysics' Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Paulo de Goes Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
Glycoconj J. 2022 Oct;39(5):653-661. doi: 10.1007/s10719-022-10061-z. Epub 2022 May 10.
At cell surface gangliosides might associate with signal transducers proteins, grown factor receptors, integrins, small G-proteins and tetraspanins establishing microdomains, which play important role in cell adhesion, cell activation, motility, and growth. Previously, we reported that GM2 and GM3 form a heterodimer that interacts with the tetraspanin CD82, controlling epithelial cell mobility by inhibiting integrin-hepatocyte growth factor-induced cMet tyrosine kinase signaling. By using molecular dynamics simulations to study the molecular basis of GM2/GM3 interaction we demonstrate, here, that intracellular levels of Ca mediate GM2/GM3 complexation via electrostatic interaction with their carboxyl groups, while hydrogen bonds between the ceramide groups likely aid stabilizing the complex. The presence of GM2/GM3 complex alters localization of CD82 on cell surface and therefore downstream signalization. These data contribute for the knowledge of how glycosylation may control signal transduction and phenotypic changes.
在细胞膜表面，神经节苷脂可能与信号转导蛋白、生长因子受体、整合素、小 G 蛋白和四跨膜蛋白结合，形成微区，在细胞黏附、细胞激活、运动和生长中发挥重要作用。先前，我们报道 GM2 和 GM3 形成异二聚体，与四跨膜蛋白 CD82 相互作用，通过抑制整合素-肝细胞生长因子诱导的 cMet 酪氨酸激酶信号转导来控制上皮细胞的迁移能力。在这里，我们通过分子动力学模拟研究 GM2/GM3 相互作用的分子基础，证明细胞内 Ca 水平通过与它们的羧基的静电相互作用介导 GM2/GM3 复合物的形成，而神经酰胺基团之间的氢键可能有助于稳定复合物。GM2/GM3 复合物的存在改变了 CD82 在细胞表面的定位，从而改变下游信号转导。这些数据有助于了解糖基化如何控制信号转导和表型变化。
