2QA0

Structure of Adeno-Associated virus serotype 8

2QA0 の概要

• エントリーDOI: 10.2210/pdb2qa0/pdb
• 分子名称: Capsid protein, SODIUM ION (3 entities in total)
• 機能のキーワード: beta-barrel, icosahedral virus, virus
• 由来する生物種: Adeno-associated virus - 8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58551.36

構造登録者

Nam, H.-J. (登録日: 2007-06-14, 公開日: 2008-04-08, 最終更新日: 2023-08-30)

主引用文献

Nam, H.J.,Lane, M.D.,Padron, E.,Gurda, B.,McKenna, R.,Kohlbrenner, E.,Aslanidi, G.,Byrne, B.,Muzyczka, N.,Zolotukhin, S.,Agbandje-McKenna, M.
Structure of adeno-associated virus serotype 8, a gene therapy vector.
J.Virol., 81:12260-12271, 2007

PubMed Abstract: Adeno-associated viruses (AAVs) are being developed as gene therapy vectors, and their efficacy could be improved by a detailed understanding of their viral capsid structures. AAV serotype 8 (AAV8) shows a significantly greater liver transduction efficiency than those of other serotypes, which has resulted in efforts to develop this virus as a gene therapy vector for hemophilia A and familial hypercholesterolemia. Pseudotyping studies show that the differential tissue tropism and transduction efficiencies exhibited by the AAVs result from differences in their capsid viral protein (VP) amino acids. Towards identifying the structural features underpinning these disparities, we report the crystal structure of the AAV8 viral capsid determined to 2.6-A resolution. The overall topology of its common overlapping VP is similar to that previously reported for the crystal structures of AAV2 and AAV4, with an eight-stranded beta-barrel and long loops between the beta-strands. The most significant structural differences between AAV8 and AAV2 (the best-characterized serotype) are located on the capsid surface at protrusions surrounding the two-, three-, and fivefold axes at residues reported to control transduction efficiency and antibody recognition for AAV2. In addition, a comparison of the AAV8 and AAV2 capsid surface amino acids showed a reduced distribution of basic charge for AAV8 at the mapped AAV2 heparin sulfate receptor binding region, consistent with an observed non-heparin-binding phenotype for AAV8. Thus, this AAV8 structure provides an additional platform for mutagenesis efforts to characterize AAV capsid regions responsible for differential cellular tropism, transduction, and antigenicity for these promising gene therapy vectors.

PubMed: 17728238
DOI: 10.1128/JVI.01304-07

実験手法

X-RAY DIFFRACTION (2.6 Å)