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HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.
Nature Communications ( IF 16.6 ) Pub Date : 2018-03-16 , DOI: 10.1038/s41467-018-03565-6
Daniela Fera 1 , Matthew S Lee 1 , Kevin Wiehe 2, 3 , R Ryan Meyerhoff 3, 4 , Alessandro Piai 5 , Mattia Bonsignori 2, 3 , Baptiste Aussedat 6 , William E Walkowicz 6 , Therese Ton 7 , Jeffrey O Zhou 8 , Samuel Danishefsky 6 , Barton F Haynes 2, 3 , Stephen C Harrison 1, 9
Affiliation  

HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man9-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs-the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.

中文翻译:

HIV外壳V3区模拟物体现了广泛中和的抗体谱系表位的关键特征。

HIV-1包膜(Env)模拟物是预防性疫苗和潜在疗法的候选成分。在这里,我们使用合成的V3-糖肽(“ Man 9 -V3”)进行HIV Env第三可变环(V3)-聚糖定向,广泛中和抗体(bnAb)谱系(“ DH270”)的结构研究,以观察表位在Env上进行研究,并研究血统的亲和力成熟度如何进行。与以前的许多V3模仿者不同,Man 9-V3包含被V3-聚糖bnAbs识别的V3区域的两个关键特征-保守的GDIR基序和N332聚糖。在我们的谱系成员DH270.6的抗体片段与V3糖肽复合的结构中,与抗体结合的糖肽的构象与完整HIV-1 Env三聚体中相应片段的构象非常接近。额外的结构可确定宽度发展过程中两个关键突变的作用。结果提示了使用V3糖肽作为疫苗免疫原的策略。
更新日期:2018-03-16
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