Interactions of Adeno-associated virus (AAV) with its Cellular Receptor, RAAV
EMSL Project ID
51225
Abstract
AAV is a leading vector for gene therapy, and, through genomic screening, we recently identified the cellular receptor, AAVR. Biochemistry, and early cryo-EM indicate that the different serotype variants have evolved to emphasize interactions with different receptor domains. AAVR interactions with four serotypes, and chimeric mutants, will be visualized with cryo-EM at resolutions of 2-3 Å, to ascertain how the differential cell specificities of different AAVs are mediated. For the most part, structures will be determined by single particle analysis (SPA), assisted by application of icosahedral symmetry. A pipeline is in place for generation of (non-infectious) virus-like particles (VLPs) and receptor domain fragments, with strong preliminary data indicating tractability of the cryo-EM. For selected parts of the receptor that appear smeared, attempts will be made to resolve conformations that deviate from the virus’ icosahedral symmetry, using focused sub-volume reconstruction.
Project Details
Start Date
2019-12-20
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members