3raa

Structural studies of AAV8 capsid transitions associated with endosomal trafficking

spinqualitylabelsall models 3raa, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3raa is a 1 chain structure with sequence from Adeno-associated virus - 8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: AMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8JQF8_9VIRU Publication Abstract from PubMed The ssDNA parvoviruses enter host cells through receptor-mediated endocytosis and infection depends on processing in the early to late endosome as well as the lysosome prior to nuclear entry for replication. However, the mechanisms of capsid endosomal processing, including the effects of low pH, are poorly understood. To gain insight into the structural transitions required for this essential step in infection, the crystal structures of empty and GFP gene packaged Adeno-associated virus (AAV) serotype 8 (AAV8) has been determined at pHs 6.0, 5.5, and 4.0, and then at 7.5 after incubation at 4.0, mimicking the conditions encountered during endocytic trafficking. While the capsid viral protein (VP) topologies of all the structures were similar, significant amino acid side-chain conformational rearrangements were observed on (I) the interior surface of the capsid under the icosahedral three-fold axis near ordered nucleic acid density that was lost concomitant with the conformational change as pH was reduced and (II) the exterior capsid surface close to the icosahedral two-fold depression. The three-fold change is consistent with DNA release from an ordering interaction on the inside surface of the capsid at low pH and suggests transitions that likely trigger the capsid for genome uncoating. The surface change results in disruption of VP:VP interface interactions and a decrease in buried surface area between VP monomers. This disruption points to capsid destabilization which may (I) release VP1 amino acids for its phospholipase A2 function for endosomal escape and nuclear localization signals for nuclear targeting and (II) trigger genome uncoating. Structural studies of AAV8 capsid transitions associated with endosomal trafficking.,Nam HJ, Gurda BL, McKenna R, Potter M, Byrne B, Salganik M, Muzyczka N, Agbandje-McKenna M J Virol. 2011 Sep 7. PMID:21900159 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures

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