The Yeager laboratory has almost two decades of experience using high resolution electron cryomicroscopy (cryoEM) and image processing to explore the molecular design of large, multicomponent supramolecular assemblies, primarily viruses and membrane proteins. Viruses that have been examined include those that cause significant human disease (HIV-1, rotavirus, SARS, hepatitis B, and arenaviruses) and nonhuman pathogens that have been particularly useful for exploring general principles of virus assembly (retroviruses such as murine leukemia virus (MLV), reoviruses, sobemoviruses, nodaviruses, tetraviruses, and tobamoviruses). The eukaryotic membrane proteins that have been studied play important roles in physiology, such as cell-to-cell communication (gap junction channels), water transport (aquaporins), and transmembrane signaling (integrins).

Together with Pat Brown and Alan Rein, he showed that immature MLV lacks strict icosahedral symmetry but does exhibit paracrystalline hexagonal packing. This cryoEM analysis showed that maturation of MLV involves a dramatic reorganization of the packing arrangements within the ribonucleoprotein core, with disordering and loosening of the individual protein components. Together with Wes Sundquist, he performed a 3D reconstruction of 2D crystals of MLV CA that revealed a hexameric lattice, similar in design to HIV-1 and Rous sarcoma virus CA. In a 2004 study with the Rein Lab, the effects of blocking individual maturation cleavages in Gag were examined. The results suggested that generation of free NC may be required to allow the NC conformational changes that confer RNA chaperone activity. Most recently, his lab has derived the first higher resolution map of hexagonal 2D crystals of full-length HIV-1 CA. Three important protein-protein assembly interfaces are required for capsid formation. Each CA hexamer is composed of an inner ring of six N-terminal domains and an outer ring of C-terminal domains that form dimeric linkers connecting neighboring hexamers. Interactions between the two domains of CA further stabilize the hexamer and provide a structural explanation for the mechanism of action of known HIV-1 assembly inhibitors.

The collaborations between the Yeager and Sundquist labs have been spearheaded by Dr. Barbie Ganser-Pornillos, who is manager of the EM Crystallography Core.