9MIV

Native tagless Lassa virus spike complex pH 6.0

9MIV の概要

• エントリーDOI: 10.2210/pdb9miv/pdb
• EMDBエントリー: 48303
• 分子名称: Glycoprotein G2, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (15 entities in total)
• 機能のキーワード: spike complex, viral protein
• 由来する生物種: Lassa virus Josiah; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 339760.82

構造登録者

Katz, M.,Cohen-Dvashi, H.,Diskin, R. (登録日: 2024-12-13, 公開日: 2025-08-27, 最終更新日: 2025-09-24)

主引用文献

Katz, M.,Cohen-Dvashi, H.,Borni, S.,Ruedas, J.,Henkel, G.,McCormack, K.,Diskin, R.
pH-induced conformational changes and inhibition of the Lassa virus spike complex.
Cell Host Microbe, 33:1577-1588.e7, 2025

PubMed Abstract: Lassa virus (LASV) is a devastating human pathogen with no vaccines and limited therapeutics. The LASV class-I spike complex engages target cells via binding its primary host receptor, matriglycan, followed by macropinocytosis and binding of its secondary receptor, lysosomal-associated membrane protein 1 (LAMP1), to trigger virus fusion. This process occurs across multiple pH-dependent steps, but the molecular events remain largely unknown. Through high-resolution structures, we study the pH-induced conformational changes of the spike preceding membrane fusion. We reveal pH-sensitive metal coordination sites that control the integrity of the spike's native state, elucidate a reorganization of the spike's transmembrane region, and provide a mechanism for dissociation from its primary receptor. Using the entry inhibitor ARN-75039, we validate our findings and establish the molecular basis for the binding and function of this investigational drug. These data define the molecular basis for the cell entry of LASV and will promote efforts in combating this virus and potentially related viral pathogens.

PubMed: 40897176
DOI: 10.1016/j.chom.2025.07.020

実験手法

ELECTRON MICROSCOPY (2.02 Å)