Skip to main content
eScholarship
Open Access Publications from the University of California

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

  • Author(s): Tan, Yong Zi
  • Aiyer, Sriram
  • Mietzsch, Mario
  • Hull, Joshua A
  • McKenna, Robert
  • Grieger, Joshua
  • Samulski, R Jude
  • Baker, Timothy S
  • Agbandje-McKenna, Mavis
  • Lyumkis, Dmitry
  • et al.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View