Michael G. Rossmann (1930–2019): Leadership in structural biology for 60 years

Michael Rossmann passed away on May 14, 2019 at nearly 89 years of age following a courageous 5-year fight with cancer. During that time he maintained the arduous schedule of laboratory leadership, preparing grant proposals (he had four R01 NIH grants at the time of his death), traveling and publishing that characterized his previous 55 years in structural biology. Although there were many medical challenges associated with his illness few people were aware of the monumental effort that was required to maintain the “Rossmann persona” that we saw at conferences and gatherings during that time. He would not have appreciated that descriptor because it implies a pretense. His “persona” came from doing the best science possible in his unique style and demanding the same from others. Many graduate students, post docs, and principal investigators recall the penetrating questions (putting it nicely) that Michael would raise during presentations at conferences, graduate student committee meetings and seminars. His passion was maintained to the end. Three weeks before he died he was working on manuscripts and grant proposals and there were already six publications in print for 2019. The first word that comes to mind when colleagues talk about Michael is energy. Throughout his life he exuded mental and physical energy and a passion for getting things done. The second word is impatience. Things rarely happened fast enough for Michael because he could not imagine others lacking the same gifts, focus, and discipline that he had. This could lead to edginess in interactions with lab members, collaborators, and administrators and Michael frequently experienced frustration with those around him, myself included. The upside for those on the receiving end was motivation, accomplishments, and exceptionally good science; the downside was sleepless nights when you were not living up to expectation. Meetings of lab alumni and collaborators often result in sharing “special moments” of dealing with these aspects of Michael G. Rossmann. The other side of Michael contrasts dramatically with the description earlier. He could be warm, considerate, and compassionate with colleagues, providing insightful, nonscientific, advice, as I experienced during difficult times in my personal and professional life. There is widespread respect from those that worked with Michael or knew him well and gratitude for how he shaped our professional lives. Forty years after leaving his lab his opinion of my choice and execution of projects was still very important to me. What follows is a commentary, mostly in chronological order, on some of Michael's contributions to structural biology most of which are easily found by going to PubMed and following the 446 (of over 600 total) publications listed there. I finish with some personal remembrances of times with Michael. Michael's contributions to structural biology span 60 years and started when he joined the Medical Research Council (MRC) laboratory of Max Perutz in 1958. He made pivotal contributions to the structure determination of hemoglobin and, with David Blow, developed the practical approaches that lead to the widespread use of molecular replacement (MR). The 1962 rotation function paper was prescient in describing the use of noncrystallographic symmetry (NCS) applied to virus structure determination, well before high resolution crystallographic data were collected from virus crystals. Rossmann moved from the MRC to the Department of Biological Sciences at Purdue University in 1964. Henry Koefler, the head of Biosciences at Purdue, was determined to build a molecular biology department and recruiting Rossmann was a high priority. The laboratory was running in a short time and produced the structure of dogfish Lactate Dehydrogenase (LDH) in 1970, one of the largest, early protein structures determined. Ironically the subunits formed a functional enzyme with 222 symmetry, but the symmetry site was on a crystallographic 222 site, so NCS could not be used in the structure determination. Three years later Rossmann's group determined the structure of lobster Glyceraldehyde-3-Phosphate Dehydrogenase (GPD), employing NCS 222 symmetry locate heavy atoms and to improve the multiple isomorphous replacement (MIR) phases. Rossmann immediately recognized the conserved nucleotide-binding site in GPD when compared to LDH (I recall arriving at the lab the morning after the team had spent the night tracing the GPD chain and seeing “GPD is LDH” on the blackboard) (Figure 1). The paper describing the Rossmann Received: 24 June 2019 Accepted: 24 June 2019