8SG7

Adeno-Associated Virus Bat origin capsid protein basic regions in complex with importin-alpha 2

8SG7 の概要

• エントリーDOI: 10.2210/pdb8sg7/pdb
• 分子名称: Importin subunit alpha-1, VP1 capsid (3 entities in total)
• 機能のキーワード: importin, alpha, adeno associated, complex, basic regions, transport, nucleus, transport protein
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61523.60

構造登録者

Hoad, M.,Forwood, J.K. (登録日: 2023-04-11, 公開日: 2023-07-19, 最終更新日: 2024-03-20)

主引用文献

Hoad, M.,Roby, J.A.,Forwood, J.K.
Structural basis for nuclear import of bat adeno-associated virus capsid protein.
J.Gen.Virol., 105:-, 2024

PubMed Abstract: Adeno-associated viruses (AAV) are one of the world's most promising gene therapy vectors and as a result, are one of the most intensively studied viral vectors. Despite a wealth of research into these vectors, the precise characterisation of AAVs to translocate into the host cell nucleus remains unclear. Recently we identified the nuclear localization signals of an AAV porcine strain and determined its mechanism of binding to host importin proteins. To expand our understanding of diverse AAV import mechanisms we sought to determine the mechanism in which the Cap protein from a bat-infecting AAV can interact with transport receptor importins for translocation into the nucleus. Using a high-resolution crystal structure and quantitative assays, we were able to not only determine the exact region and residues of the N-terminal domain of the Cap protein which constitute the functional NLS for binding with the importin alpha two protein, but also reveal the differences in binding affinity across the importin-alpha isoforms. Collectively our results allow for a detailed molecular view of the way AAV Cap proteins interact with host proteins for localization into the cell nucleus.

PubMed: 38441555
DOI: 10.1099/jgv.0.001960

実験手法

X-RAY DIFFRACTION (2.4 Å)