Divergent engagements between adeno-associated viruses with their cellular receptor AAVR

Nat Commun. 2019 Aug 21;10(1):3760. doi: 10.1038/s41467-019-11668-x.

Abstract

Adeno-associated virus (AAV) receptor (AAVR) is an essential receptor for the entry of multiple AAV serotypes with divergent rules; however, the mechanism remains unclear. Here, we determine the structures of the AAV1-AAVR and AAV5-AAVR complexes, revealing the molecular details by which PKD1 recognizes AAV5 and PKD2 is solely engaged with AAV1. PKD2 lies on the plateau region of the AAV1 capsid. However, the AAV5-AAVR interface is strikingly different, in which PKD1 is bound at the opposite side of the spike of the AAV5 capsid than the PKD2-interacting region of AAV1. Residues in strands F/G and the CD loop of PKD1 interact directly with AAV5, whereas residues in strands B/C/E and the BC loop of PKD2 make contact with AAV1. These findings further the understanding of the distinct mechanisms by which AAVR recognizes various AAV serotypes and provide an example of a single receptor engaging multiple viral serotypes with divergent rules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid / metabolism*
  • Capsid / ultrastructure
  • Capsid Proteins / classification
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism
  • Dependovirus / classification
  • Dependovirus / genetics
  • Dependovirus / physiology*
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Image Processing, Computer-Assisted
  • Protein Binding
  • Protein Conformation
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cell Surface / ultrastructure
  • Serogroup
  • TRPP Cation Channels
  • Transduction, Genetic
  • Virus Internalization*

Substances

  • Capsid Proteins
  • KIAA0319L protein, human
  • Receptors, Cell Surface
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein