- EMDB-41820: Cryo-EM structure of vaccine-elicited CD4 binding site antibody D... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-41820
タイトル
Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env
マップデータ
Cryo-EM structure of rhesus macaque vaccination elicited CD4 binding site antibody DH1285 Fab bound at two CD4 binding sites on CH505TFchim.6R.SOSIP.664v4.1 Env
試料
細胞器官・細胞要素: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio
キーワード
HIV-1 / CD4 binding site antibody / Vaccine elicited antibody / neutralizing antibody / IgG / Fab / DH1285 / VIRAL PROTEIN
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 A1145687
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 A1144371
米国
引用
ジャーナル: Cell / 年: 2024 タイトル: Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques. 著者: Kevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / ...著者: Kevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / Joena Bal / Nicholas Havill / Haiyan Chen / Emily Machiele / Nolan Jamieson / Bhavna Hora / Megan Kopp / Katarzyna Janowska / Kara Anasti / Chuancang Jiang / Elizabeth Van Itallie / Sravani Venkatayogi / Amanda Eaton / Rory Henderson / Christopher Barbosa / S Munir Alam / Sampa Santra / Drew Weissman / M Anthony Moody / Derek W Cain / Ying K Tam / Mark Lewis / Wilton B Williams / Kevin Wiehe / David C Montefiori / Priyamvada Acharya / Barton F Haynes / 要旨: The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs ...The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.
ダウンロード / ファイル: emd_41820.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Cryo-EM structure of rhesus macaque vaccination elicited CD4 binding site antibody DH1285 Fab bound at two CD4 binding sites on CH505TFchim.6R.SOSIP.664v4.1 Env
全体 : A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env...
全体
名称: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio
要素
細胞器官・細胞要素: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio
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超分子 #1: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env...
超分子
名称: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0
由来(天然)
生物種: Human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
分子量
理論値: 300 KDa
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実験情報
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構造解析
手法
クライオ電子顕微鏡法
解析
単粒子再構成法
試料の集合状態
particle
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試料調製
濃度
1.3 mg/mL
緩衝液
pH: 8
凍結
凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 298 K / 装置: LEICA EM CPC
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 59.1 e/Å2