Seeing engineered loops in a gene delivery vehicle by cryoEM

Abstract

In this issue of Structure, Lerch and colleagues present a 4.5 Å cryo electron microscopy (cryoEM) structure of a variant of an adeno-associated virus that has been genetically engineered for liver gene therapy. The identification of two structurally distinct loops flanking the highly conserved jellyroll β barrel highlights the potentials of high-resolution cryoEM.

Figure 1. CryoEM structure of AAV-DJ and comparison with X-ray structures of naturally occurring AAV

(A) Ribbon representation of the AAV-DJ subunit atomic model, colored by amino-acid residue number (N and C termini are blue and orange, respectively). Side chains are shown as sticks for the VR-I and VR-IV loops. (B, C) Zoom-in views of the VR-I loop (B) and VR-IV loop (C), with the AAV-2 (purple ribbon) (Xie et al., 2002) and AAV-8 (cyan ribbon) (Nam et al., 2007) X-ray models superimposed. (D, E) Regions of the 4.5Å AAV-DJ density map (gray mesh) superimposed with its atomic model (sticks).