Investigating conformational dynamics of viral capsids with electron cryo microscopy

Description

lectron microscopy and image processing are important tools for structure determination of large complexes. In the last couple of years tremendous progress has been made in the design of electron microscopes and detectors as well as in image processing. It is now possible to obtain structures at 3-4 Å resolution from vitrified complexes without the necessity of having crystals. In many cases it turns out that complexes are intrinsically heterogeneous and structures of the distinct conformational and/or compositional states can be determined. However, often complexes are dynamically flexible, which ultimately limits the resolution. In my talk I will give a brief overview of the method. Then I will show how Hepatitis B cores change their conformation upon phosphorylation. The transition of phosphorylated to unphosphorylated capsids coincides with capsids becoming competent for envelopment. However, it has been difficult to reconcile how an alteration at a disordered region in the inside of a capsid can control envelopment at the outside of the capsid. I will show that small conformational changes in the helical arrangement of the protein provide a possible route of structural communication between the inside and the outside. Finally I will also present our recent structure of a premature envelopment mutant at 4.5 Å resolution.

Period	17 Jun 2014
Held at	University of Stuttgart