6WFT

BatAAV-10HB - genome-containing particles

これはPDB形式変換不可エントリーです。

6WFT の概要

• エントリーDOI: 10.2210/pdb6wft/pdb
• EMDBエントリー: 21656
• 分子名称: VP1 capsid, 2'-DEOXYADENOSINE-5'-MONOPHOSPHATE (2 entities in total)
• 機能のキーワード: icosahedral capsid, aav, gene therapy, non-primate, bat, virus
• 由来する生物種: Bat adeno-associated virus
• タンパク質・核酸の鎖数: 60
• 化学式量合計: 3484335.66

構造登録者

Mietzsch, M.,Agbandje-McKenna, M. (登録日: 2020-04-04, 公開日: 2020-06-24, 最終更新日: 2025-05-14)

主引用文献

Mietzsch, M.,Li, Y.,Kurian, J.,Smith, J.K.,Chipman, P.,McKenna, R.,Yang, L.,Agbandje-McKenna, M.
Structural characterization of a bat Adeno-associated virus capsid.
J.Struct.Biol., 211:107547-107547, 2020

PubMed Abstract: Adeno-associated viruses (AAVs) are widespread among vertebrates. AAVs isolated from bats display low capsid protein sequence identities (<60%) to AAV2, AAV5, and other primate AAVs. Here we report the first capsid structure of a non-primate AAV which was isolated from bats. The capsid structure of BtAAV-10HB (10HB) was determined by cryo-electron microscopy and three-dimensional image reconstruction to 3.03 Å resolution. Comparison of empty and genome-containing capsids showed that the capsid structures are almost identical except for an ordered nucleotide in a previously described nucleotide-binding pocket, the density in the 5-fold channel, and several amino acids with altered side chain conformations. Compared to other dependoparvoviruses, for example AAV2 and AAV5, 10HB displays unique structural features including insertions and deletions in capsid surface loops. Overall, the 10HB capsid structure superposes with an RMSD of 1.7 Å and 1.8 Å to AAV2 and AAV5, respectively. Currently all approved AAV human gene therapy biologics and vectors in clinical trials are based on primate isolates. However, pre-existing neutralizing antibodies in the human population represents a hurdle to their use. 10HB capsids are capable of packaging AAV2 vector genomes and thus have potential as gene delivery vectors. Significantly, a screen with human sera showed lack of recognition by the 10HB capsid. Thus, the different capsid surface of 10HB vectors likely renders it "invisible" to potential pre-existing neutralizing human anti-AAV antibodies especially because this virus or similar variants do not exist in primate populations.

PubMed: 32522552
DOI: 10.1016/j.jsb.2020.107547

実験手法

ELECTRON MICROSCOPY (3.03 Å)