Solution Structures of Engineered Vault Particles
Solution Structures of Engineered Vault Particles
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DOI：
10.1016/j.str.2018.02.014
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发表时间：
2018-04-03
期刊：
影响因子：
5.7
通讯作者：
Zhou, Z. Hong
中科院分区：
文献类型：
--
作者：
Ding, Ke;Zhang, Xing;Zhou, Z. Hong
先前的拱顶晶体结构已经提供了其结构变异性的线索，但由于晶体堆积的原因，还不是结论性的。在这里，我们通过在大鼠主要穹窿蛋白（MVP）的 N 末端工程化 HIV-1 Gag 蛋白片段获得了穹窿，并在溶液/非晶体环境中确定了它们的近原子分辨率（类似于 4.8 A 度）结构。溶液中的桶形拱顶采用两种构象1和2，均具有D39对称性。从 N 端到 C 端，每个 MVP 单体具有三个区域：主体、肩部和帽子。虽然构象 1 与其中一种晶体结构相同，但构象 2 中的肩部纵向易位达 10 埃，从而形成向外突出的帽。我们的结构澄清了先前晶体学模型中身体区域的结构差异。该拱顶的药物输送潜力通过其位于工程拱顶桶腰部的 Gag 加载 N 端延伸部分的内部配置和结构灵活性而凸显。
Prior crystal structures of the vault have provided clues of its structural variability but are non-conclusive due to crystal packing. Here, we obtained vaults by engineering at the N terminus of rat major vault protein (MVP) an HIV-1 Gag protein segment and determined their near-atomic resolution (similar to 4.8 A degrees) structures in a solution/non-crystalline environment. The barrel-shaped vaults in solution adopt two conformations, 1 and 2, both with D39 symmetry. From the N to C termini, each MVP monomer has three regions: body, shoulder, and cap. While conformation 1 is identical to one of the crystal structures, the shoulder in conformation 2 is translocated longitudinally up to 10 angstrom, resulting in an outward-projected cap. Our structures clarify the structural discrepancies in the body region in the prior crystal-lography models. The vault's drug-delivery potential is highlighted by the internal disposition and structural flexibility of its Gag-loaded N-terminal extension at the barrel waist of the engineered vault.