M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen (Fg) that, unlike M1 or Fg alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the M1-Fg complex. A conformationally dynamic coiled-coil dimer of M1 was found to organize four Fg molecules into a specific cross-like pattern. This pattern supported the construction of a supramolecular network that was required for neutrophil activation but was distinct from a fibrin clot. Disruption of this network into other supramolecular assemblies was not tolerated. These results have bearing on the pathophysiology of streptococcal toxic shock.

Sulfolobus turreted icosahedral virus (STIV) was isolated in acidic hot springs where it infects the archeon Sulfolobus solfataricus . We determined the STIV structure using near-atomic resolution electron microscopy and X-ray crystallography allowing tracing of structural polypeptide chains and visualization of transmembrane proteins embedded in the viral membrane. We propose that the vertex complexes orchestrate virion assembly by coordinating interactions of the membrane and various protein components involved. STIV shares the same coat subunit and penton base protein folds as some eukaryotic and bacterial viruses, suggesting that they derive from a common ancestor predating the divergence of the three kingdoms of life. One architectural motif (β-jelly roll fold) forms virtually the entire capsid (distributed in three different gene products), indicating that a single ancestral protein module may have been at the origin of its evolution.

Summary We applied whole cell electron cryotomography to the archaeon Sulfolobus infected by Sulfolobus turreted icosahedral virus (STIV), which belongs to the PRD1-Adeno lineage of dsDNA viruses. STIV infection induced the formation of pyramid-like protrusions with sharply defined facets on the cell surface. They had a thicker cross-section than the cytoplasmic membrane and did not contain an exterior surface protein layer (S-layer). Intra-pyramidal bodies often occupied the volume of the pyramids. Mature virions, procapsids without genome cores, and partially assembled particles were identified, suggesting that the capsid and inner membrane co-assemble in the cytoplasm to form a procapsid. A two-class reconstruction using a maximum likelihood algorithm demonstrated that no dramatic capsid transformation occurred upon DNA packaging. Virions tended to form tightly packed clusters or quasi-crystalline arrays while procapsids mostly scattered outside or on the edges of the clusters. The study revealed vivid images of STIV assembly, maturation and particle distribution in cell.

Aims Next-generation targeted nanodevices are currently under development for imaging and therapeutic applications. We engineered HK97 viral nanoparticles (VNPs) for tumor cell-specific targeting. Methods A combination of genetic and chemical engineering methods were developed and applied to generate dual-labeled HK97 cysteine mutant particles displaying transferrin and fluorescent labels. The targeting properties of transferrin-conjugated VNPs were evaluated by in vitro experiments using different cancer cell lines. Results We found that HK97–tranferrin formulations were indeed targeted to cancer cells in vitro via the transferrin receptor. These studies highlight the utility and facilitate the further development of HK97-based VNPs.