EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	pH-induced conformational changes and inhibition of the Lassa virus spike complex.
ジャーナル・号・ページ	Cell Host Microbe, Vol. 33, Issue 9, Page 1577-11588.e7, Year 2025
掲載日	2025年9月10日
著者	Michael Katz / Hadas Cohen-Dvashi / Sarah Borni / John Ruedas / Greg Henkel / Ken McCormack / Ron Diskin /
PubMed 要旨	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, ...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.
リンク	Cell Host Microbe / PubMed:40897176
手法	EM (単粒子)
解像度	1.9 - 3.3 Å
構造データ	48275 9mhe EMDB-48275, PDB-9mhe: Native tagless Lassa virus spike complex bound to ARN-75039 at pH 8.0 手法: EM (単粒子) / 解像度: 2.01 Å 48303 9miv EMDB-48303, PDB-9miv: Native tagless Lassa virus spike complex pH 6.0 手法: EM (単粒子) / 解像度: 2.02 Å 48305 9miy EMDB-48305, PDB-9miy: Focused reconstruction of the transmembrane region of the Lassa virus spike complex 手法: EM (単粒子) / 解像度: 2.72 Å 48306 9mj1 EMDB-48306, PDB-9mj1: Native tagless Lassa virus spike complex bound at pH 8.0 手法: EM (単粒子) / 解像度: 1.9 Å 48307 9mj2 EMDB-48307, PDB-9mj2: Flag-tag Lassa virus spike complex at pH 6.0 手法: EM (単粒子) / 解像度: 2.58 Å 48308 9r8u EMDB-48308: Map of LASV spike complex after exposure to pH 5.0 and re-equilibration to pH 8.0 PDB-9r8u: Flag-tag LASV spike acidified to pH 5.0 and re-equilibrated to pH 8.0 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-48309: LASV spike complex bound to ARN-75039 at pH 6.0 手法: EM (単粒子) / 解像度: 3.22 Å EMDB-53842: LASV tagless in complex with 12.1F Fab reconstructed at C1 手法: EM (単粒子) / 解像度: 1.99 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-UNX: Unknown entry PDB-1bk9: PHOSPHOLIPASE A2 MODIFIED BY PBPB ChemComp-HOH: WATER
由来	lassa virus josiah (ウイルス) homo sapiens (ヒト)
キーワード	VIRAL PROTEIN / Spike complex