6NZ0

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

Summary for 6NZ0

• Entry DOI: 10.2210/pdb6nz0/pdb
• EMDB information: 0553 0621 0622 0623 0624
• Descriptor: Dyslexia-associated protein KIAA0319-like protein, Capsid protein VP1, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: aav, aavr, receptor, coreceptor, virus, kiaa0319l, pkd, parvovirus
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 113939.13

Authors

Meyer, N.L.,Xie, Q.,Davulcu, O.,Yoshioka, C.,Chapman, M.S. (deposition date: 2019-02-12, release date: 2019-06-12, Last modification date: 2024-10-16)

Primary citation

Meyer, N.L.,Hu, G.,Davulcu, O.,Xie, Q.,Noble, A.J.,Yoshioka, C.,Gingerich, D.S.,Trzynka, A.,David, L.,Stagg, S.M.,Chapman, M.S.
Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR.
Elife, 8:-, 2019

PubMed Abstract: 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. -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. -electron microscopy with a two-domain receptor fragment reveals the interactions at 2.4 Å 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.

PubMed: 31115336
DOI: 10.7554/eLife.44707

Experimental method

ELECTRON MICROSCOPY (2.4 Å)