3.5Å cryoEM Structure of Hepatitis B Virus Core Assembled from Full-Length Core Protein
News Sep 24, 2013
The capsid shell of infectious hepatitis B virus (HBV) is composed of 240 copies of a single protein called HBV core antigen (HBc). An atomic model of a core assembled from truncated HBc was determined previously by X-ray crystallography. In an attempt to obtain atomic structural information of HBV core in a near native, non-crystalline environment, we reconstructed a 3.5Å-resolution structure of a recombinant core assembled from full-length HBc by cryo electron microscopy (cryoEM) and derived an atomic model. The structure shows that the 240 molecules of full-length HBc form a core with two layers. The outer layer, composed of the N-terminal assembly domain, is similar to the crystal structure of the truncated HBc, but has three differences. First, unlike the crystal structure, our cryoEM structure shows no disulfide bond between the Cys61 residues of the two subunits within the dimer building block, indicating such bond is not required for core formation. Second, our cryoEM structure reveals up to four more residues in the linker region (amino acids 140-149). Third, the loops in the cryoEM structures containing this linker region in subunits B and C are oriented differently (~30° and ~90°) from their counterparts in the crystal structure. The inner layer, composed of the C-terminal arginine-rich domain (ARD) and the ARD-bound RNAs, is partially-ordered and connected with the outer layer through linkers positioned around the two-fold axes. Weak densities emanate from the rims of positively charged channels through the icosahedral three-fold and local three-fold axes. We attribute these densities to the exposed portions of some ARDs, thus explaining ARD’s accessibility by proteases and antibodies. Our data supports a role of ARD in mediating communication between inside and outside of the core during HBV maturation and envelopment.
This article was published online in PLoS One and is free to access.
Homemade Microscope Reveals How Viruses Cling to Our DNANews
Using a homemade, high-tech microscope, scientists at the School of Medicine have revealed how a cancer-causing virus anchors itself to our DNA. That discovery could pave the way for doctors to cure incurable diseases by flushing out viruses, including HPV and Epstein-Barr, that now permanently embed themselves in our cells.READ MORE
Neuropeptide Y Y1 Receptor Structure Solved, Offers New Opportunities for Anti-obesity Drug DiscoveryNews
Scientists solve the crystal structure of Neuropeptide Y Y1 Receptor, offering new opportunities for anti-obesity drug discovery.READ MORE
Crystal Structure of Neuropeptide 1 Receptor Solved, Providing Therapeutic Angle For Obesity TreatmentNews
An international team has uncovered the potential to beat obesity at the cellular level, characterizing for the first time a complex, little-understood receptor type that, when activated, shuts off hunger.READ MORE