Jack Johnson

Johnson obtained his Ph.D. in physical (X-ray crystallography) and inorganic chemistry from Iowa State University in 1972 and immediately changed fields to structural virology during a 6-year post doc with Michael Rossmann at Purdue. Johnson was part of the Rossmann team that determined the structure of southern bean mosaic virus (SBMV) in 1980, following the publication of tomato bushy stunt virus (TBSV) structure by the Harrison group at Harvard in 1978. The fold of the shell forming protein domain (virus jellyroll) of SBMV was superimposable on the fold of TBSV. At the time, this was a shocking result. The amino acid sequences available (determined from the proteins) were diXerent, yet the folds were nearly identical. The result was an early indicator of the limited number of folds in the protein universe and certainly foretold the commonality of the jellyroll in many diXerent RNA and DNA viruses. Johnson joined the faculty at Purdue in 1978 and determined virus structures with crystallography. The subunit structure of the first insect virus (Black Beetle Virus) had the jellyroll fold, but as recognized later, used the viral genome as a molecular switch to form the quasi-equivalent capsid. The structure of cowpea mosaic virus (CPMV) revealed an ordered segment of RNA and suggested the topology of genome packaging. In collaboration with George LomonnossoX at the John Innes Center (UK) CPMV became a protype for virusbased nanotechnology. Collaboration with electron microscopist Tim Baker at Purdue provided a moderate resolution image of a monoclonal Fab fragment bound to CPMV, allowing a detailed description of the virus epitope.

The Johnson lab’s move to Scripps Research in 1995 changed their focus to mechanistic structural virology. Mass spectrometry showed that animal virus particles were highly dynamic with internal regions (determined later to be lytic peptides) transiently exposed and such exposure was required for infectivity. Mechanisms for viral subunit autocatalytic cleavages and subunit ligations in tailed dsDNA bacteriophages were confirmed. Structures of the latter revealed a remarkable “chain mail” topology providing extraordinary particle stability. Archeal viruses infecting sulfolobus in Yellowstone hot springs and having a mass of 13 mega Daltons were studied with crystallography, cryoEM and tomography, revealing the structural subunits (jellyrolls), alterations to host cells by infection and in vivo assembly. Prior to the lab closing and extended into Johnson’s retirement the focus is on virus maturation, the process by which an initial capsid assembly product (procapsid) undergoes precise structural transitions to yield an infectious virion. These studies of phage and eukaryotic viruses required stable intermediates to fully understand the processes and they were obtained by mutation or carefully controlling electrostatic conditions in vitro. Phage maturation studies revealed subunit refolding, Brownian ratchets and adjustment of the particle energy landscape through proteolysis. Eukaryotic maturation was controlled by the electrostatic environment within the cell and resulted in a 100Å change in particle dimension, subunit refolding with the formation of an autocatalytic cleavage site and unique functions of quasi-equivalent subunits. Johnson recently relocated to West Lafayette.