8XH7

Structure of EBV LMP1 oligomer

Summary for 8XH7

• Entry DOI: 10.2210/pdb8xh7/pdb
• EMDB information: 38343
• Descriptor: Latent membrane protein 1 (1 entity in total)
• Functional Keywords: ebv latent membrane protein 1, viral protein
• Biological source: human gammaherpesvirus 4 (HHV-4, Human herpesvirus 4)
• Total number of polymer chains: 6
• Total formula weight: 112376.51

Authors

Gao, P.,Huang, J.F. (deposition date: 2023-12-17, release date: 2024-06-26, Last modification date: 2024-09-18)

Primary citation

Huang, J.,Zhang, X.,Nie, X.,Zhang, X.,Wang, Y.,Huang, L.,Geng, X.,Li, D.,Zhang, L.,Gao, G.,Gao, P.
Assembly and activation of EBV latent membrane protein 1.
Cell, 187:4996-5009.e14, 2024

PubMed 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 decades of extensive research, the molecular basis for LMP1 folding, assembly, and activation remains unclear. Here, we report cryo-electron microscopy structures of LMP1 in two unexpected assemblies: a symmetric homodimer and a higher-order filamentous oligomer. LMP1 adopts a non-canonical and unpredicted fold that supports the formation of a stable homodimer through tight and antiparallel intermolecular packing. LMP1 dimers further assemble side-by-side into higher-order filamentous oligomers, thereby allowing the accumulation and specific organization of the flexible cytoplasmic tails for efficient recruitment of downstream factors. Super-resolution microscopy and cellular functional assays demonstrate that mutations at both dimeric and oligomeric interfaces disrupt LMP1 higher-order assembly and block multiple LMP1-mediated signaling pathways. Our research provides a framework for understanding the mechanism of LMP1 and for developing potential therapies targeting EBV-associated diseases.

PubMed: 38996527
DOI: 10.1016/j.cell.2024.06.021

Experimental method

ELECTRON MICROSCOPY (3.52 Å)