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首页> 外文期刊>Journal of Molecular Biology >Conformational changes in adeno-associated virus type 1 induced by genome packaging.
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Conformational changes in adeno-associated virus type 1 induced by genome packaging.

机译：由基因组包装引起的1型腺伴随病毒的构象变化。

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摘要

Adeno-associated virus (AAV) is frequently used as a vector for gene therapy. The viral capsid consists of three structural proteins (VP1, VP2, and VP3) that have a common C-terminal core (VP3), with N-terminal extensions of increasing length in VP2 and VP1. The capsid encloses a single-stranded genome of up to 4.7 kb, which is packaged into empty capsids. The N-terminal extension of VP1 carries a phospholipase domain that becomes accessible during infection in the endosomal pathway. We have used cryo-electron microscopy and image reconstruction to determine subnanometer-resolution structures of recombinant AAV1 that has packaged different amounts of a 3.6-kb recombinant genome. The maps show that the AAV1 capsid undergoes continuous conformational changes upon packaging of the genome. The rearrangements occur at the inner capsid surface and lead to constrictions of the pores at the 5-fold symmetry axes and to subtle movements of the beta-sheet regions of the capsid proteins. In fully packaged particles, the genome forms stem-like features that contact the inner capsid surface at the 3-fold symmetry axes. We think that the reorganization of the inner surface has an impact on the viral life cycle during infection, preparing the externalization of phospholipase domains through the pores at the 5-fold symmetry axes and possibly genome release.
机译：腺相关病毒（AAV）经常用作基因治疗的载体。病毒衣壳由三个结构蛋白（VP1，VP2和VP3）组成，它们具有共同的C端核心（VP3），并且N端延伸的VP2和VP1长度不断增加。衣壳包含一个长达4.7 kb的单链基因组，该基因组被包装成空衣壳。 VP1的N端延伸带有一个磷脂酶结构域，该酶在内体途径的感染过程中变得可访问。我们已经使用了冷冻电子显微镜和图像重建来确定重组AAV1的亚纳米分辨率结构，该结构包装了不同量的3.6 kb重组基因组。这些图表明，AAV1衣壳在基因组包装后经历连续的构象变化。重排发生在衣壳内部表面，并导致孔在5倍对称轴上收缩，并导致衣壳蛋白β-折叠区域的微妙运动。在完全包装的颗粒中，基因组会形成茎状特征，并在3倍对称轴上与内部衣壳表面接触。我们认为内表面的重组对感染过程中的病毒生命周期有影响，准备通过5倍对称轴上的孔使磷脂酶结构域外化，并可能释放基因组。

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