ジャーナル: Cell Host Microbe / 年: 2023 タイトル: IFITM3 blocks influenza virus entry by sorting lipids and stabilizing hemifusion. 著者: Steffen Klein / Gonen Golani / Fabio Lolicato / Carmen Lahr / Daniel Beyer / Alexia Herrmann / Moritz Wachsmuth-Melm / Nina Reddmann / Romy Brecht / Mehdi Hosseinzadeh / Androniki Kolovou / ...著者: Steffen Klein / Gonen Golani / Fabio Lolicato / Carmen Lahr / Daniel Beyer / Alexia Herrmann / Moritz Wachsmuth-Melm / Nina Reddmann / Romy Brecht / Mehdi Hosseinzadeh / Androniki Kolovou / Jana Makroczyova / Sarah Peterl / Martin Schorb / Yannick Schwab / Britta Brügger / Walter Nickel / Ulrich S Schwarz / Petr Chlanda / 要旨: Interferon-induced transmembrane protein 3 (IFITM3) inhibits the entry of numerous viruses through undefined molecular mechanisms. IFITM3 localizes in the endosomal-lysosomal system and specifically ...Interferon-induced transmembrane protein 3 (IFITM3) inhibits the entry of numerous viruses through undefined molecular mechanisms. IFITM3 localizes in the endosomal-lysosomal system and specifically affects virus fusion with target cell membranes. We found that IFITM3 induces local lipid sorting, resulting in an increased concentration of lipids disfavoring viral fusion at the hemifusion site. This increases the energy barrier for fusion pore formation and the hemifusion dwell time, promoting viral degradation in lysosomes. In situ cryo-electron tomography captured IFITM3-mediated arrest of influenza A virus membrane fusion. Observation of hemifusion diaphragms between viral particles and late endosomal membranes confirmed hemifusion stabilization as a molecular mechanism of IFITM3. The presence of the influenza fusion protein hemagglutinin in post-fusion conformation close to hemifusion sites further indicated that IFITM3 does not interfere with the viral fusion machinery. Collectively, these findings show that IFITM3 induces lipid sorting to stabilize hemifusion and prevent virus entry into target cells.
ダウンロード / ファイル: emd_15705.map.gz / 形式: CCP4 / 大きさ: 390.9 MB / タイプ: IMAGE STORED AS SIGNED BYTE
注釈
Tomogram of A549 cell.
ボクセルのサイズ
X=Y=Z: 10.3 Å
密度
最小 - 最大
-128.0 - 127.0
平均 (標準偏差)
31.694965 (±21.066770000000002)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
96
51
-61
サイズ
1815
1947
116
Spacing
1947
1815
116
セル
A: 20054.1 Å / B: 18694.5 Å / C: 1194.8 Å α=β=γ: 90.0 °
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添付データ
-
試料の構成要素
-
全体 : A549 cell
全体
名称: A549 cell
要素
細胞: A549 cell
-
超分子 #1: A549 cell
超分子
名称: A549 cell / タイプ: cell / ID: 1 / 親要素: 0
由来(天然)
生物種: Homo sapiens (ヒト)
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実験情報
-
構造解析
手法
ネガティブ染色法, クライオ電子顕微鏡法
解析
電子線トモグラフィー法
試料の集合状態
cell
-
試料調製
緩衝液
pH: 7.4
染色
タイプ: POSITIVE / 材質: 0.1 % uranyl acetate (UA)
糖包埋
材質: Lowicryl HM20 resin
凍結
凍結剤: NITROGEN
加圧凍結法
装置: OTHER 詳細: The value given for _em_high_pressure_freezing.instrument is Leica automated freeze substitution system AFS2. This is not in a list of allowed values {'LEICA EM HPM100', 'LEICA EM PACT', 'BAL- ...詳細: The value given for _em_high_pressure_freezing.instrument is Leica automated freeze substitution system AFS2. This is not in a list of allowed values {'LEICA EM HPM100', 'LEICA EM PACT', 'BAL-TEC HPM 010', 'LEICA EM PACT2', 'EMS-002 RAPID IMMERSION FREEZER', 'OTHER'} so OTHER is written into the XML file.