Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site.
Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site.
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DOI：
10.1038/nsmb.3291
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发表时间：
2016-10
影响因子：
16.8
通讯作者：
Bjorkman, Pamela J.
中科院分区：
文献类型：
--
作者：
Gristick, Harry B.;von Boehmer, Lotta;West, Anthony P., Jr.;Schamber, Michael;Gazumyan, Anna;Golijanin, Jovana;Seaman, Michael S.;Faetkenheuer, Gerd;Klein, Florian;Nussenzweig, Michel C.;Bjorkman, Pamela J.
HIV-1疫苗设计通过结构研究来了解，这些结构研究阐明了广泛中和抗体（bNAb）识别和/或容纳三聚体包膜糖蛋白（Env）上的N-聚糖的机制。高甘露糖和复合型Env糖型的变异性导致异质性，这通常妨碍天然聚糖盾的可视化。我们提出了具有完全加工和天然糖基化的HIV-1 Env三聚体的3.5-ε-和3.9-ε-分辨率晶体结构，揭示了高甘露糖和复合型N-聚糖的聚糖屏蔽，我们使用它来定义两个bNAb的完整表位。Env三聚体与10-1074（针对V3环）和IOMA（一种新的CD 4结合位点（CD 4 bs）抗体）复合。尽管IOMA源自VH 1 -2*02（CD 4 bs靶向VRC 01类bNAb的种系基因），但其轻链缺乏定义VRC 01类bNAb的短CDRL 3。因此，IOMA类似于8ANC 131类/VH 1 -46衍生的CD 4 b bNAb，其具有正常长度的CDRL 3。组合了VRC 01类和8ANC 131类抗体的联合收割机特征的bNAb的存在对于靶向VRC 01样bNAb的免疫策略具有意义。
HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-Å- and 3.9-Å-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46–derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.
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影响因子：
16.8
作者：
Kong, Leopold;Lee, Jeong Hyun;Doores, Katie J.;Murin, Charles D.;Julien, Jean-Philippe;McBride, Ryan;Liu, Yan;Marozsan, Andre;Cupo, Albert;Klasse, Per-Johan;Hoffenberg, Simon;Caulfield, Michael;King, C. Richter;Hua, Yuanzi;Le, Khoa M.;Khayat, Reza;Deller, Marc C.;Clayton, Thomas;Tien, Henry;Feizi, Ten;Sanders, Rogier W.;Paulson, James C.;Moore, John P.;Stanfield, Robyn L.;Burton, Dennis R.;Ward, Andrew B.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
DOI：
10.1126/science.1259206
发表时间：
2014-12-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McGuire AT;Dreyer AM;Carbonetti S;Lippy A;Glenn J;Scheid JF;Mouquet H;Stamatatos L
通讯作者：
Stamatatos L
影响因子：
16.6
作者：
Lee JH;Leaman DP;Kim AS;Torrents de la Peña A;Sliepen K;Yasmeen A;Derking R;Ramos A;de Taeye SW;Ozorowski G;Klein F;Burton DR;Nussenzweig MC;Poignard P;Moore JP;Klasse PJ;Sanders RW;Zwick MB;Wilson IA;Ward AB
通讯作者：
Ward AB
DOI：
10.1016/j.str.2015.07.020
发表时间：
2015-10-06
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Lee JH;de Val N;Lyumkis D;Ward AB
通讯作者：
Ward AB
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH