Structure determination of an anti-HIV-1 Fab 447-52D-peptide complex from an epitaxially twinned data set
Structure determination of an anti-HIV-1 Fab 447-52D-peptide complex from an epitaxially twinned data set
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DOI：
10.1107/s0907444908013978
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发表时间：
2008-07-01
影响因子：
2.2
通讯作者：
Wilson, Ian A.
中科院分区：
文献类型：
--
作者：
Dhillon, Amandeep K.;Stanfield, Robyn L.;Wilson, Ian A.
尽管针对HIV-1病毒包膜糖蛋白第三可变环（V3）的抗体是在感染者体内检测到的首批中和抗体之一，但它们的特异性通常受到限制。V3特异性抗体的x射线晶体学研究有助于更彻底地了解对该表位的识别和V3环中的保守特征，这可能有助于设计多组分疫苗。与其他V3-loop抗体相比，人抗体447-52D对初级病毒分离物表现出相对广泛的中和作用。在2.1埃分辨率下测定了Fab 447-52D与V3肽（UG1033）配合物的晶体结构。该结构是使用外延孪晶数据集和内部程序来检测和去除重叠反射来确定的。虽然处理后的数据的完整性低于预期，分辨率略高于正常R值，但获得了高质量的电子密度图，从而可以确定结构。该结构揭示了一个扩展的CDR H3环，该环与肽形成β -片，主要接触是主链氢键。V3肽和Fab与先前报道的其他Fab 447-52D复合物的结构具有高度的结构同源性，这加强了V3环可能采用一小组保守结构的观点，特别是在β发夹冠周围。
Although antibodies against the third variable loop ( V3) of the HIV-1 viral envelope glycoprotein are among the first neutralizing antibodies to be detected in infected individuals, they are normally restricted in their specificity. X-ray crystallographic studies of V3-specific antibodies have contributed to a more thorough understanding of recognition of this epitope and of conserved features in the V3 loop that could potentially aid in the design of a multi-component vaccine. The human antibody 447-52D exhibits relatively broad neutralization of primary viral isolates compared with other V3-loop antibodies. A crystal structure of Fab 447-52D in complex with a V3 peptide ( UG1033) was determined at 2.1 angstrom resolution. The structure was determined using an epitaxially twinned data set and in-house programs to detect and remove overlapping reflections. Although the processed data have lower than desired completeness and slightly higher than normal R values for the resolution, good-quality electron-density maps were obtained that enabled structure determination. The structure revealed an extended CDR H3 loop that forms a beta-sheet with the peptide, with the predominant contacts being main-chain hydrogen bonds. The V3 peptide and Fab show high structural homology with the previously reported structures of other Fab 447-52D complexes, reinforcing the idea that the V3 loop may adopt a small set of conserved structures, particularly around the crown of the beta-hairpin.