Protolytic and conformational control of virus capsid maturation: the bacteriophage HK97 system

Bacteriophage capsid assembly pathways provide excellent model systems1Laboratory of Structural to study large-scale conformational changes and other mechanisms thatBiology, National Institute of Arthritis, Musculoskeletal and regulate the formation of macromolecular complexes. These capsids are formed from proheads: relatively fragile precursor particles which matureSkin Diseases, National Institutes of Health, Bethesda by undergoing extensive remodeling. Phage HK97 employs novel features in its strategy for building capsids, including assembly without a scaffoldingMD 20892-2755, USA protein, and the formation of a network of covalent cross-links between2Department of Biological neighboring subunits in the mature virion. In addition, proteolytic cleavage Sciences, University of of the capsid protein from 42 kDa to 31 kDa is essential for maturation. To Pittsburgh, Pittsburgh investigate the structural bases for proteolysis and cross-linking, we have PA 15260, USA used cryo-electron micrographs to reconstruct the three-dimensional structures of purified particles from four discrete stages in the assembly pathway: Prohead I, Prohead II, Head I and Head II. Prohead I has icosahedral T = 7 packing of blister-shaped pentamers and hexamers. The pentamers are 5-fold symmetric, but the hexamers exhibit an unusual departure from 6-fold symmetry, as if two trimers had undergone a shea