6nz0

Cryo-EM structure of AAV-2 in complex with AAVR PKD domains 1 and 2

Loading... Status: waiting for Mol* initialization Structural highlights 6nz0 is a 2 chain structure with sequence from Adeno-associated virus 2 Srivastava/1982 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.4Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Adeno-associated virus (AAV) vectors are preeminent in emerging clinical gene therapies. Generalizing beyond the most tractable genetic diseases will require modulation of cell specificity and immune neutralization. Interactions of AAV with its cellular receptor, AAVR, are key to understanding cell-entry and trafficking with the rigor needed to engineer tissue-specific vectors. Cryo-electron tomography shows ordered binding of part of the flexible receptor to the viral surface, with distal domains in multiple conformations. Regions of the virus and receptor in close physical proximity can be identified by cross-linking/mass spectrometry. Cryo-electron microscopy with a two-domain receptor fragment reveals the interactions at 2.4 A resolution. AAVR binds between AAV's spikes on a plateau that is conserved, except in one clade whose structure is AAVR-incompatible. AAVR's footprint overlaps the epitopes of several neutralizing antibodies, prompting a re-evaluation of neutralization mechanisms. The structure provides a roadmap for experimental probing and manipulation of viral-receptor interactions. Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR.,Meyer NL, Hu G, Davulcu O, Xie Q, Noble AJ, Yoshioka C, Gingerich DS, Trzynka A, David L, Stagg SM, Chapman MS Elife. 2019 May 22;8. pii: 44707. doi: 10.7554/eLife.44707. PMID:31115336 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures

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