2024年7月11日出版的《细胞》杂志发表了科学家的一项最新研究成果。中国科学院生物物理研究所高璞、高光侠和张立国课题组报道了EBV潜伏膜蛋白1的组装与激活。

课题组人员报道了潜伏膜蛋白1在两个意想不到的组装中的低温电子显微镜结构：对称的同型二聚体和高阶的丝状低聚体。潜伏膜蛋白1采用非经典和不可预测的折叠，支持通过紧密和反平行的分子间包装形成稳定的同型二聚体。潜伏膜蛋白1二聚体进一步并排组装成高阶丝状低聚物，从而允许灵活的细胞质尾部的积累和特定组织，以有效地招募下游因子。

超高分辨率显微镜和细胞功能分析表明，二聚体和寡聚体界面的突变都会破坏潜伏膜蛋白1的高阶组装，并阻断多种潜伏膜蛋白1介导的信号通路。他们的研究为理解潜伏膜蛋白1的机制，和开发针对EB病毒(相关疾病的潜在疗法提供了一个框架。

据悉，潜伏膜蛋白1 (Latent membrane protein 1, LMP1)是EB病毒(EBV)的主要致癌蛋白，在EBV的生命周期和发病机制中起着多种作用。尽管经过数十年的广泛研究，潜伏膜蛋白1折叠、组装和激活的分子基础仍不清楚。

附：英文原文

Title: Assembly and activation of EBV latent membrane protein 1

Author: Jiafeng Huang, Xiaolin Zhang, Xiaohua Nie, Xuyuan Zhang, Yong Wang, Linlong Huang, Xiaohan Geng, Dong Li, Liguo Zhang, Guangxia Gao, Pu Gao

Issue&Volume: 2024-07-11

Abstract: Latent membrane protein 1 (LMP1) is the primary oncoprotein of Epstein-Barr virus(EBV) and plays versatile roles in the EBV life cycle and pathogenesis. Despite decadesof extensive research, the molecular basis for LMP1 folding, assembly, and activationremains unclear. Here, we report cryo-electron microscopy structures of LMP1 in twounexpected assemblies: a symmetric homodimer and a higher-order filamentous oligomer.LMP1 adopts a non-canonical and unpredicted fold that supports the formation of astable homodimer through tight and antiparallel intermolecular packing. LMP1 dimersfurther assemble side-by-side into higher-order filamentous oligomers, thereby allowingthe accumulation and specific organization of the flexible cytoplasmic tails for efficientrecruitment of downstream factors. Super-resolution microscopy and cellular functionalassays demonstrate that mutations at both dimeric and oligomeric interfaces disruptLMP1 higher-order assembly and block multiple LMP1-mediated signaling pathways. Ourresearch provides a framework for understanding the mechanism of LMP1 and for developingpotential therapies targeting EBV-associated diseases.

DOI: 10.1016/j.cell.2024.06.021

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00695-0