Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene.
Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene.
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DOI：
10.1016/j.chom.2018.09.010
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发表时间：
2018-10-10
影响因子：
30.3
通讯作者：
Wilson IA
中科院分区：
文献类型：
--
作者：
Wu NC;Yamayoshi S;Ito M;Uraki R;Kawaoka Y;Wilson IA
针对流感血凝素（HA）干的广泛中和抗体（bnAb）的发现和表征为通用流感疫苗的开发提供了见解。识别来自不同个体的bnAb共有的特征将是指导免疫原设计的关键。S9-3-37是从健康H5 N1疫苗接种者中分离的bnAb。在此，结构表征揭示了S9-3-37的D3-9基因区段贡献了与HA上高度保守的茎表位的大部分相互作用表面。与其他流感bnAb晶体结构的比较表明，D3-9区段提供了靶向HA茎的一般机制。有趣的是，这种bnAb可以以非常不同的角度和方向接近HA股骨柄。此外，D3-9可以在不同的bnAb中以不同的阅读框翻译，但仍然靶向相同的HA柄袋。因此，人免疫库中的D3-9基因区段可以提供针对流感病毒的强大防御。确定了与流感血凝素干细胞结合的bnAb S9-3-37的结构，S9-3-37的D3-9编码区贡献了与HA的大部分相互作用表面，S9-3-37的D3-9基因片段可以在两个不同的阅读框中接合HA干细胞。9基因片段代表抗体靶向HA茎的重复机制bnAbs是通用流感疫苗设计的关键。Wu等人报道，流感血凝素干细胞靶向bnAb的D3-9编码区段贡献了大部分相互作用表面，并且是靶向血凝素干细胞的抗体中的重复基序。
Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus. Structure of bnAb S9-3-37 bound to influenza hemagglutinin stem was determined D3-9-encoded region of S9-3-37 contributes majority of the interaction surface with HA D3-9 gene segment of S9-3-37 can engage the HA stem in two different reading frames D3-9 gene segment represents a recurring mechanism for antibody targeting of HA stem Identifying signature features common to broadly neutralizing antibodies (bnAbs) is key to universal flu vaccine design. Wu et al. report that the D3-9 encoded segment of an influenza hemagglutinin stem-targeting bnAb contributes the majority of the interaction surface and is a recurring motif in antibodies that target the hemagglutinin stem.
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影响因子：
64.8
作者：
Chevalier A;Silva DA;Rocklin GJ;Hicks DR;Vergara R;Murapa P;Bernard SM;Zhang L;Lam KH;Yao G;Bahl CD;Miyashita SI;Goreshnik I;Fuller JT;Koday MT;Jenkins CM;Colvin T;Carter L;Bohn A;Bryan CM;Fernández-Velasco DA;Stewart L;Dong M;Huang X;Jin R;Wilson IA;Fuller DH;Baker D
通讯作者：
Baker D
影响因子：
14.9
作者：
Eroshkin AM;LeBlanc A;Weekes D;Post K;Li Z;Rajput A;Butera ST;Burton DR;Godzik A
通讯作者：
Godzik A
影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC
DOI：
10.1073/pnas.1319058110
发表时间：
2014-01-07
影响因子：
11.1
作者：
Friesen, Robert H. E.;Lee, Peter S.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
影响因子：
3.7
作者：
Gorny, Miroslaw K.;Pan, Ruimin;Zolla-Pazner, Susan
通讯作者：
Zolla-Pazner, Susan