National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
米国
引用
ジャーナル: Cell Host Microbe / 年: 2020 タイトル: Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site. 著者: Laura A Powell / Andrew Miller / Julie M Fox / Nurgun Kose / Thomas Klose / Arthur S Kim / Robin Bombardi / Rashika N Tennekoon / A Dharshan de Silva / Robert H Carnahan / Michael S Diamond / ...著者: Laura A Powell / Andrew Miller / Julie M Fox / Nurgun Kose / Thomas Klose / Arthur S Kim / Robin Bombardi / Rashika N Tennekoon / A Dharshan de Silva / Robert H Carnahan / Michael S Diamond / Michael G Rossmann / Richard J Kuhn / James E Crowe / 要旨: Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease ...Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections.
フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) 平均電子線量: 30.0 e/Å2
電子線
加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN
電子光学系
C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 倍率(公称値): 18000
試料ステージ
ホルダー冷却材: NITROGEN
実験機器
モデル: Titan Krios / 画像提供: FEI Company
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画像解析
初期モデル
モデルのタイプ: OTHER
最終 再構成
想定した対称性 - 点群: I (正20面体型対称) / 解像度のタイプ: BY AUTHOR / 解像度: 5.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: jspr / 使用した粒子像数: 18410
初期 角度割当
タイプ: RANDOM ASSIGNMENT
最終 角度割当
タイプ: PROJECTION MATCHING / ソフトウェア - 名称: jspr
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原子モデル構築 1
精密化
プロトコル: RIGID BODY FIT
得られたモデル
PDB-6w1c: Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain