4rso | pdb_00004rso

The structure of the neurotropic AAVrh.8 viral vector

spinqualitylabelsall models 4rso, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rso is a 1 chain structure with sequence from Non-human primate Adeno-associated virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q808Y3_9VIRU Publication Abstract from PubMed Adeno-associated virus rhesus isolate 8 (AAVrh.8) is a leading vector for the treatment of neurological diseases due to its efficient transduction of neuronal cells and reduced peripheral tissue tropism. Toward identification of the capsid determinants for these properties, the structure of AAVrh.8 was determined by X-ray crystallography to 3.5 A resolution and compared to those of other AAV isolates. The capsid viral protein (VP) structure consists of an alphaA helix and an eight-stranded anti-parallel beta-barrel core conserved in parvoviruses, and large insertion loop regions between the beta-strands form the capsid surface topology. The AAVrh.8 capsid exhibits the surface topology conserved in all AAVs: depressions at the icosahedral twofold axis and surrounding the cylindrical channel at the fivefold axis, and three protrusions around the threefold axis. A structural comparison to serotypes AAV2, AAV8, and AAV9, to which AAVrh.8 shares approximately 84%, approximately 91%, and approximately 87% VP sequence identity, respectively, revealed differences in the surface loops known to affect receptor binding, transduction efficiency, and antigenicity. Consistent with this observation, biochemical assays showed that AAVrh.8 is unable to bind heparin and does not cross-react with conformational monoclonal antibodies and human donor serum directed against the other AAVs compared. This structure of AAVrh.8 thus identified capsid surface differences which can serve as template regions for rational design of vectors with enhanced transduction for specific tissues and escape pre-existing antibody recognition. These features are essential for the creation of an AAV vector toolkit that is amenable to personalized disease treatment. Structure of neurotropic adeno-associated virus AAVrh.8.,Halder S, Van Vliet K, Smith JK, Duong TT, McKenna R, Wilson JM, Agbandje-McKenna M J Struct Biol. 2015 Oct;192(1):21-36. doi: 10.1016/j.jsb.2015.08.017. Epub 2015, Aug 31. PMID:26334681 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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