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Structural Characterization of Porcine Adeno-Associated Virus Capsid Protein with Nuclear Trafficking Protein Importin Alpha Reveals a Bipartite Nuclear Localization Signal

Viruses. 2023-01; 
Mikayla Hoad, Emily M Cross, Camilla M Donnelly, Subir Sarker, Justin A Roby, Jade K Forwood
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Proteins, Expression, Isolation and Analysis … This can be attributed to the inability of AAVs to replicate in host cells without the co-… coli and cloned into the pGEX4T-1 vector (GenScript, USA) at BamHI sites with an additional N-… Get A Quote

摘要

Adeno-associated viruses (AAV) are important vectors for gene therapy, and accordingly, many aspects of their cell transduction pathway have been well characterized. However, the specific mechanisms that AAV virions use to enter the host nucleus remain largely unresolved. We therefore aimed to reveal the interactions between the AAV Cap protein and the nuclear transport protein importin alpha (IMPα) at an atomic resolution. Herein we expanded upon our earlier research into the Cap nuclear localization signal (NLS) of a porcine AAV isolate, by examining the influence of upstream basic regions (BRs) towards IMPα binding. Using a high-resolution crystal structure, we identified that the IMPα binding determinant... More

關鍵詞

Adeno-associated virus, binding interface, importin alpha, nuclear localization, structure
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