Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features.
Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features.
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完成AAV结构图谱：血清型衣壳结构揭示进化枝特异性特征。
DOI：
10.3390/v13010101
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发表时间：
2021-01-13
期刊：
影响因子：
--
通讯作者：
Agbandje-McKenna M
中科院分区：
文献类型：
--
作者：
Mietzsch M;Jose A;Chipman P;Bhattacharya N;Daneshparvar N;McKenna R;Agbandje-McKenna M
大多数腺相关病毒（AAV）血清型的衣壳结构已经被确定为抗原分支。本研究报道了AAV7、AAV11、AAV12和AAV13的剩余衣壳结构，分别通过冷冻电子显微镜和三维图像重建到2.96、2.86、2.54和2.76 Å分辨率。这些结构完成了AAV血清型衣壳的结构图谱。AAV7代表第一进化枝D衣壳结构；AAV11和AAV12属于目前未分配的分支，其中包括AAV4；AAV13为第一个AAV2-AAV3杂化枝C衣壳结构。这些新确定的衣壳结构都表现出AAV衣壳的特征，包括5倍通道、3倍突出、2倍凹陷和一个核苷酸结合袋，其中包含一个有序的核苷酸。然而，这些结构具有病毒蛋白，显示进化枝特异性环构象。这种结构表征完成了我们当前AAV血清型的三维库，提供了与衣壳组装兼容的表面环结构图谱，并适用于未来的载体工程工作。衍生载体在特定组织靶向、转导效率、抗原性或受体重靶向方面可以提高基因传递的成功率。
The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
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影响因子：
5.4
作者：
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通讯作者：
Agbandje-McKenna, Mavis
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
2.7
作者：
Blackburn, SD;Steadman, RA;Johnson, FB
通讯作者：
Johnson, FB