6CBE

Atomic structure of a rationally engineered gene delivery vector, AAV2.5

This is a non-PDB format compatible entry.

Summary for 6CBE

• Entry DOI: 10.2210/pdb6cbe/pdb
• EMDB information: 7452
• Descriptor: Capsid protein VP1 (1 entity in total)
• Functional Keywords: aav, dependoparvovirus, gene therapy vector, retional design, virus
• Biological source: Adeno-associated virus 2
• Total number of polymer chains: 60
• Total formula weight: 4921039.68

Authors

Burg, M.,Rosebrough, C.,Drouin, L.,Bennett, A.,Mietzsch, M.,Chipman, P.,McKenna, R.,Sousa, D.,Potter, M.,Byrne, B.,Kozyreva, O.G.,Samulski, R.J.,Agbandje-McKenna, M. (deposition date: 2018-02-02, release date: 2018-05-30, Last modification date: 2025-05-28)

Primary citation

Burg, M.,Rosebrough, C.,Drouin, L.M.,Bennett, A.,Mietzsch, M.,Chipman, P.,McKenna, R.,Sousa, D.,Potter, M.,Byrne, B.,Jude Samulski, R.,Agbandje-McKenna, M.
Atomic structure of a rationally engineered gene delivery vector, AAV2.5.
J. Struct. Biol., 203:236-241, 2018

PubMed Abstract: AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 Å using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2.5 residues exchanged from AAV2 to AAV1, Q263A, T265 (insertion), N706A, V709A, and T717N, were readily interpretable. Significantly, the surface loops containing these residues adopt the AAV1 conformation indicating the importance of amino acid residues in dictating VP structure.

PubMed: 29775653
DOI: 10.1016/j.jsb.2018.05.004

Experimental method

ELECTRON MICROSCOPY (2.78 Å)