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-Structure paper
タイトル | Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20. |
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ジャーナル・号・ページ | Virology, Vol. 431, Issue 1-2, Page 40-49 |
掲載日 | 2012年6月9日 |
著者 | Dustin M McCraw / Jason K O'Donnell / Kenneth A Taylor / Scott M Stagg / Michael S Chapman / |
PubMed 要旨 | The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5Å resolution is determined for ...The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5Å resolution is determined for a complex of AAV-2 with the Fab' fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells. |
リンク | Virology / PubMed:22682774 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 8.5 Å |
構造データ | |
由来 |
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キーワード | VIRUS/IMMUNE SYSTEM / Epitope / Fab / gene therapy / VIRUS-IMMUNE SYSTEM complex |