Structural Characterization of the C-terminal tail of EBV LMP2A

Abstract

Epstein-Barr virus (EBV) Latent Membrane Protein 2A (LMP2A) is a transmembrane protein essential for viral latency and immune evasion, structured with distinct functional domains. The N-terminal domain modulates B-cell receptor signaling, while the transmembrane and C-terminal regions help anchor the protein and facilitate additional interactions within host cells. This study characterizes the LMP2A C-terminal domain (CTD) structure under various conditions using CD spectroscopy and NMR. The 29-residue C-tail sequence contains key residues that impact stability. CD analysis shows that, while disordered at neutral pH and in water, helicity is slightly enhanced under acidic conditions and membrane-mimicking environments, with DTT influencing stability through oxidation state effects. NMR structural analysis in DPC micelles reveals a well-converged helical structure extending from residues R471 to E486, closely matching AlphaFold predictions. The data highlight the CTD’s structural plasticity and suggest roles for cysteines and hydrophobic clusters in stabilizing the peptide in membrane-like settings.