3j1q | pdb_00003j1q

Structure of AAV-DJ, a Retargeted Gene Therapy Vector: Cryo-Electron Microscopy at 4.5A resolution

Loading... Status: waiting for Mol* initialization Structural highlights 3j1q is a 1 chain structure with sequence from Adeno-associated virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6JC41_9VIRU Publication Abstract from PubMed AAV-DJ, a leading candidate vector for liver gene therapy, was created through random homologous recombination followed by directed evolution, selecting for in vivo liver tropism and resistance to in vitro immune neutralization. Here, the 4.5 A resolution cryo-EM structure is determined for the engineered AAV vector, revealing structural features that illuminate its phenotype. The heparan sulfate receptor-binding site is little changed from AAV-2, and heparin-binding affinity is similar. A loop that is antigenic in other serotypes has a unique conformation in AAV-DJ that would conflict with the binding of an AAV-2 neutralizing monoclonal antibody. This is consistent with increased resistance to neutralization by human polyclonal sera, raising the possibility that changed tropism may be a secondary effect of altered immune interactions. The reconstruction exemplifies analysis of fine structural changes and the potential of cryo-EM, in favorable cases, to characterize mutant or ligand-bound complexes. Structure of AAV-DJ, a Retargeted Gene Therapy Vector: Cryo-Electron Microscopy at 4.5 A Resolution.,Lerch TF, O'Donnell JK, Meyer NL, Xie Q, Taylor KA, Stagg SM, Chapman MS Structure. 2012 Aug 8;20(8):1310-20. Epub 2012 Jun 21. PMID:22727812 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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