9MT2

Structure of the Machupo virus glycoprotein complex

9MT2 の概要

• エントリーDOI: 10.2210/pdb9mt2/pdb
• EMDBエントリー: 48598
• 分子名称: Pre-glycoprotein polyprotein GP complex, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: fusogen, glycoprotein, complex, membrane, viral protein
• 由来する生物種: Mammarenavirus machupoense; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 178832.84

構造登録者

Mann, C.J.,Abraham, J. (登録日: 2025-01-10, 公開日: 2025-07-16, 最終更新日: 2026-02-25)

主引用文献

Mann, C.J.,Yang, P.,Olal, D.,Fan, X.,Smith, K.N.,Clark, L.E.,Krammer, F.,Bian, Y.,Abraham, J.
Molecular organization of the New World arenavirus spike glycoprotein complex.
Nat Microbiol, 10:2207-2220, 2025

PubMed Abstract: Of the multiple arenaviruses that cause haemorrhagic fevers in the Americas, all lack reliable therapeutic options, and only one has a vaccine. The arenavirus glycoprotein complex (GPC) binds cellular receptors and mediates pH-dependent fusion of viral and host cell membranes during entry. GPC comprises GP1, GP2 and stable signal peptide (SSP) subunits. SSP remains associated with the mature glycoprotein complex and regulates pH-dependent membrane fusion through an unclear mechanism. We report cryo-EM structures of Junin virus and Machupo virus GPC stabilized in the prefusion conformation using an amino acid substitution in the transmembrane region of SSP at 3.0 Å and 2.9 Å resolution, respectively. Mutational analyses, cell-cell fusion assays and molecular dynamics simulations reveal how contacts in the membrane-proximal and transmembrane regions of GPC regulate pH-dependent membrane fusion. The structures may aid in the design of therapeutic antibody cocktails, small-molecule inhibitors and vaccines against arenaviruses.

PubMed: 40781447
DOI: 10.1038/s41564-025-02085-6

実験手法

ELECTRON MICROSCOPY (2.9 Å)