通过 NMR 探测 HIV gp120 包膜糖蛋白构象。
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
机构信息
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
出版信息
J Biol Chem. 2011 Jul 8;286(27):23975-81. doi: 10.1074/jbc.M111.251025. Epub 2011 May 18.
Abstract
The HIV envelope glycoprotein gp120 plays a critical role in virus entry, and thus, its structure is of extreme interest for the development of novel therapeutics and vaccines. To date, high resolution structural information about gp120 in complex with gp41 has proven intractable. In this study, we characterize the structural properties of gp120 in the presence and absence of gp41 domains by NMR. Using the peptide probe 12p1 (sequence, RINNIPWSEAMM), which was identified previously as an entry inhibitor that binds to gp120, we identify atoms of 12p1 in close contact with gp120 in the monomeric and trimeric states. Interestingly, the binding mode of 12p1 with gp120 is similar for clades B and C. In addition, we show a subtle difference in the binding mode of 12p1 in the presence of gp41 domains, i.e. the trimeric state, which we interpret as small differences in the gp120 structure in the presence of gp41.
摘要
HIV 包膜糖蛋白 gp120 在病毒进入中起着至关重要的作用，因此，其结构对于新型治疗药物和疫苗的开发具有极高的研究价值。迄今为止，gp120 与 gp41 复合物的高分辨率结构信息一直难以获得。在这项研究中，我们通过 NMR 技术研究了 gp120 在存在和不存在 gp41 结构域时的结构特性。我们使用先前被鉴定为与 gp120 结合的进入抑制剂的肽探针 12p1（序列：RINNIPWSEAMM），确定了 12p1 与单体和三聚体状态下 gp120 紧密结合的原子。有趣的是，12p1 与 gp120 的结合模式在 clade B 和 C 中相似。此外，我们还展示了在存在 gp41 结构域的情况下，即三聚体状态下，12p1 的结合模式存在细微差异，我们将其解释为在存在 gp41 的情况下 gp120 结构的微小差异。
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