9N0D

JUNV GP1, GP2, SSP complex with neutralizing antibody in a pseudotyped virus membrane

9N0D の概要

• エントリーDOI: 10.2210/pdb9n0d/pdb
• EMDBエントリー: 48781
• 分子名称: Pre-glycoprotein polyprotein GP complex, neutralizing antibody light chain, neutralizing antibody heavy chain, ... (8 entities in total)
• 機能のキーワード: viral protein, glycoprotein, gpc, junv, junin mammarenavirus, gp1, gp2, signal peptide, virus membrane, antibody
• 由来する生物種: Mammarenavirus juninense; 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 245355.57

構造登録者

Taylor, L.J.,Sawaya, M.R.,Castells-Graells, R.,Rodriguez, J.A. (登録日: 2025-01-24, 公開日: 2025-07-23)

主引用文献

Taylor, L.J.,Sawaya, M.R.,Westover, J.B.,Wang, C.,Jimenez, F.,Munoz, A.J.,Whitelegge, J.,Gowen, B.B.,Helguera, G.F.,Castells-Graells, R.,Rodriguez, J.A.
In situ insights into antibody-mediated neutralization of a pre-fusion Junin virus glycoprotein complex.
Cell Rep, 44:115971-115971, 2025

PubMed Abstract: A transmembrane glycoprotein complex (GPC) decorates the Junin mammarenavirus (JUNV) that causes New World hemorrhagic fevers. We leveraged single-particle cryoelectron microscopy (cryo-EM) to image the full-length JUNV GPC directly on pseudotyped virus (PV) membranes and bound by two JUNV-neutralizing antibodies: Candid#1 vaccine-elicited CR1-28 and J199, a potent therapeutic against Argentine hemorrhagic fever (AHF). The 3.8 Å resolution in situ structures of the antibody-neutralized, 3-fold symmetric JUNV GPC reveal its ectodomain architecture, signal peptide-bound transmembrane region, zinc-binding luminal domain, and post-translational modifications. JUNV-GPC sequence variants highlight the functional importance of the signal peptide transmembrane helix register for virus infection and attenuating Candid#1-associated variants. Overlapping CR1-28 and J199 epitopes suggest a common receptor-blocking mechanism for JUNV neutralization, while a J199-induced, symmetric GPC reorientation may further drive its potent inhibition of JUNV lethality in mice, compared to receptor blockade alone. This underscores the utility of in situ insights into GPC function and neutralization.

PubMed: 40632652
DOI: 10.1016/j.celrep.2025.115971

実験手法

ELECTRON MICROSCOPY (3.8 Å)