THE MAKING AND BREAKING OF SYMMETRY IN VIRUS CAPSID ASSEMBLY - GLIMPSES OF CAPSID BIOLOGY FROM CRYOELECTRON MICROSCOPY

Virus capsids constitute a diverse and versatile family of protein-bou nd containers and compartments ranging in diameter from Angstrom 200 A ngstrom (mass similar to 1 MDa) to >1500 Angstrom (mass>250 MDa). Cryo electron microscopy of capsids, now attaining resolutions down to 10 A ngstrom, is disclosing novel structural motifs, assembly mechanisms, a nd the precise locations of major epitopes. Capsids are essentially sy mmetric structures, and icosahedral surface lattices have proved to be widespread, However, many capsid proteins exhibit a remarkable propen sity for symmetry breaking, whereby chemically identical subunits in d istinct lattice sites have markedly different structures and packing r elationships. Temporal differences in the conformation of a given subu nit are also manifested in the large-scale conformational changes that accompany capsid maturation. Larger and more complex capsids, such as DNA bacteriophages and herpes simplex virus, are formed not by simple self-assembly, but under the control of tightly regulated programs th at may include the involvement of viral scaffolding proteins and cellu lar chaperonins, maturational proteolysis, and conformational changes on an epic scale. In addition to its significance for virology, capsid -related research has implications for biology in general, relating to the still largely obscure assembly processes of macromolecular comple xes that perform many important cellular functions.