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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

Team

Principal Investigator

Michael Chapman
Institution
University of Missouri - Columbia

Team Members

Grant Zane
Institution
University of Missouri - Columbia

Edward Large
Institution
University of Missouri - Columbia

Mark Silveria
Institution
University of Missouri - Columbia

Nancy Meyer
Institution
Oregon Health & Science University

Tommi White
Institution
University of Missouri - Columbia

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory