Sub-2 Å Ewald curvature corrected structure of an AAV2 capsid variant

Yong Zi Tan, Sriram Aiyer, Mario Mietzsch, Joshua A. Hull, Robert McKenna, Joshua Grieger, R. Jude Samulski, Timothy S. Baker, Mavis Agbandje-McKenna () and Dmitry Lyumkis ()
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Yong Zi Tan: New York Structural Biology Center
Sriram Aiyer: The Salk Institute for Biological Studies
Mario Mietzsch: University of Florida
Joshua A. Hull: University of Florida
Robert McKenna: University of Florida
Joshua Grieger: University of North Carolina at Chapel Hill
R. Jude Samulski: University of North Carolina at Chapel Hill
Timothy S. Baker: University of California-San Diego
Mavis Agbandje-McKenna: University of Florida
Dmitry Lyumkis: The Salk Institute for Biological Studies

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Single-particle cryogenic electron microscopy (cryo-EM) provides a powerful methodology for structural biologists, but the resolutions typically attained with experimentally determined structures have lagged behind microscope capabilities. Here, we exploit several technical advances to improve resolution, including per-particle contrast transfer function (CTF) refinement and correction for Ewald sphere curvature. The latter is demonstrated with several experimental samples and should become more standard as resolutions increase or at lower microscope accelerating voltages. The combined application of the described methods to micrographs recorded on a Titan Krios enables structure determination at ~1.86-Å resolution of an adeno-associated virus serotype 2 variant (AAV2), an important gene-delivery vehicle. The resulting structural details provide an improved model for understanding the biology of AAV that will guide future vector development for gene therapy.

Date: 2018
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DOI: 10.1038/s41467-018-06076-6

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