50 Years of structural immunology.

Fifty years ago, the first landmark structures of antibodies heralded the dawn of structural immunology. Momentum then started to build toward understanding how antibodies could recognize the vast universe of potential antigens and how antibody-combining sites could be tailored to engage antigens with high specificity and affinity through recombination of germline genes (V, D, J) and somatic mutation. Equivalent groundbreaking structures in the cellular immune system appeared some 15 to 20 years later and illustrated how processed protein antigens in the form of peptides are presented by MHC molecules to T cell receptors. Structures of antigen receptors in the innate immune system then explained their inherent specificity for particular microbial antigens including lipids, carbohydrates, nucleic acids, small molecules, and specific proteins. These two sides of the immune system act immediately (innate) to particular microbial antigens or evolve (adaptive) to attain high specificity and affinity to a much wider range of antigens. We also include examples of other key receptors in the immune system (cytokine receptors) that regulate immunity and inflammation. Furthermore, these antigen receptors use a limited set of protein folds to accomplish their various immunological roles. The other main players are the antigens themselves. We focus on surface glycoproteins in enveloped viruses including SARS-CoV-2 that enable entry and egress into host cells and are targets for the antibody response. This review covers what we have learned over the past half century about the structural basis of the immune response to microbial pathogens and how that information can be utilized to design vaccines and therapeutics.

Successes and challenges with retroviral enzymes.

Collaborations between the Wlodawer and Skalka laboratories have covered a period of almost 30 years. During that time our groups have co-authored 18 publications, including several much cited journal articles, book chapters, and scholarly reviews. It has therefore been most rewarding for us to share enthusiasm, insights, and expertise with our Frederick colleagues over the years, and also to enjoy lasting friendships.

George Minot and Pernicious Anemia.

George Minot (1885-1950) was born in Boston, Massachusetts. He was great grandson of James Jackson, co-founder of Massachusetts General Hospital in 1821. Graduating from Harvard College he enrolled at Harvard Medical School and obtained his MD in 1912. As a house pupil (intern) at the hospital he became interested in diseases of the blood and began taking meticulous histories of dietary habits of patients with anemia.

The Protein Data Bank archive as an open data resource.

The Protein Data Bank archive was established in 1971, and recently celebrated its 40th anniversary (Berman et al. in Structure 20:391, 2012). An analysis of interrelationships of the science, technology and community leads to further insights into how this resource evolved into one of the oldest and most widely used open-access data resources in biology.

Biocrystallography in Switzerland: achievements and future perspectives.

The first protein crystallography group in Switzerland was installed at the Biozentrum of the University of Basel approximately 40 years ago. Since then protein crystallography has grown and matured remarkably and is now established in the molecular biology, biochemistry or biological medicine departments of most major Swiss Universities as well as in the pharmaceutical industry and in biotech startup companies. Swiss X-ray biocrystallography groups have made remarkable contributions from the beginning and have brought Switzerland to the forefront in biostructural research during the last 5 to 10 years. Switzerland has now a leading position in the areas of supramolecular complexes, membrane proteins and structure-based drug design in pharmaceutical and biotech industries. Protein crystallography on the outer membrane protein ompF as well as the development of the lipidic cubic phase crystallization methodology has been pioneered at the Biozentrum. The latter found its somewhat late recognition through the recent explosion in structure determinations of the seven transmembrane helix G-coupled receptors. Highlights from Swiss structural biology groups in the field of supramolecular complexes include the structures of ribosomal particles, of the nucleosome and the pilus assembly complex of uropathogenic E. coli. On the membrane protein side advances in the field of ABC transporters and ion channels are world-recognized achievements of Swiss structural biology. Dedicated laboratories at many academic and industrial institutions, their current research programs, the availability of excellent infrastructure and the continuing efforts to build new facilities such as the SwissFEL indicate an even brighter future for structural biology in Switzerland.

Crystallography, evolution, and the structure of viruses.

My undergraduate education in mathematics and physics was a good grounding for graduate studies in crystallographic studies of small organic molecules. As a postdoctoral fellow in Minnesota, I learned how to program an early electronic computer for crystallographic calculations. I then joined Max Perutz, excited to use my skills in the determination of the first protein structures. The results were even more fascinating than the development of techniques and provided inspiration for starting my own laboratory at Purdue University. My first studies on dehydrogenases established the conservation of nucleotide-binding structures. Having thus established myself as an independent scientist, I could start on my most cherished ambition of studying the structure of viruses. About a decade later, my laboratory had produced the structure of a small RNA plant virus and then, in another six years, the first structure of a human common cold virus. Many more virus structures followed, but soon it became essential to supplement crystallography with electron microscopy to investigate viral assembly, viral infection of cells, and neutralization of viruses by antibodies. A major guide in all these studies was the discovery of evolution at the molecular level. The conservation of three-dimensional structure has been a recurring theme, from my experiences with Max Perutz in the study of hemoglobin to the recognition of the conserved nucleotide-binding fold and to the recognition of the jelly roll fold in the capsid protein of a large variety of viruses.

Molecular chirality: language, history, and significance.

In this chapter some background material concerning molecular chirality and enantiomerism is presented. First some basic chemical-molecular aspects of chirality are reviewed, after which certain relevant terminology whose use in the literature has been problematic is discussed. Then an overview is provided of some of the early discoveries that laid the foundations of the science of molecular chirality in chemistry and biology, including the discovery of the phenomenon of molecular chirality by L. Pasteur, the proposals for the asymmetric carbon atom by J.H. van 't Hoff and J.A. Lebel, Pasteur's discovery of biological enantioselectivity, the discovery of enantioselectivity at biological receptors by A. Piutti, the studies of enzymatic stereoselectivity by E. Fischer, and the work on enantioselectivity in pharmacology by A. Cushny. Finally, the role of molecular chirality in pharmacotherapy and new-drug development, arguably one of the main driving forces for the current intense interest in the phenomenon of molecular chirality, is discussed.

Notes of a protein crystallographer: the legacy of J.-B. J. Fourier - crystallography, time and beyond.

The importance of the Fourier transform as a fundamental tool for crystallography is well known in the field. However, the complete legacy of Jean-Baptiste Joseph Fourier (1768-1830) as a pioneer Egyptologist and premier mathematician and physicist of his time, and the implications of his work in other scientific fields, is less well known. Significantly, his theoretical and experimental work on phenomena related to the transmission of heat founded the mathematical study of irreversible phenomena and introduced the flow of time in physico-chemical processes and geology, with its implications for biological evolution. Fourier's insights are discussed in contrast to the prevalent notion of reversible dynamic time in the early 20th century, which was dominated by Albert Einstein's (1875-1953) theory of general relativity versus the philosophical notion of durée proposed by the French philosopher Henri-Louis Bergson (1859-1941). The current status of the mathematical description of irreversible processes by Ilya Romanovich Prigogine (1917-2003) is briefly discussed as part of the enduring legacy of the pioneering work of J.-B. J. Fourier, first established nearly two centuries ago, in numerous scientific endeavors.

Dr. Alexander Wlodawer-celebrating five decades of service to the structural biology community.

This 75th birthday tribute to our Editorial Board member Alexander Wlodawer recounts his decades-long service to the community of structural biology researchers. His former and current colleagues tell the story of his upbringing and education, followed by an account of his dedication to quality and rigor in crystallography and structural science. The FEBS Journal Editor-in-Chief Seamus Martin further highlights Alex's outstanding contributions to the journal's success over many years.

Michael G. Rossmann (1930-2019), pioneer in macromolecular and virus crystallography: scientist, mentor and friend.

Michael George Rossmann, who made monumental contributions to science, passed away peacefully in West Lafayette, Indiana on 14 May 2019 at the age of 88, following a courageous five-year battle with cancer. Michael was born in Frankfurt, Germany on 30 July 1930. As a young boy, he emigrated to England with his mother just as World War II ignited. Michael was a highly innovative and energetic person, well known for his intensity, persistence and focus in pursuing his research goals. Michael was a towering figure in crystallography as a highly distinguished faculty member at Purdue University for 55 years. Michael made many seminal contributions to crystallography in a career that spanned the entirety of structural biology, beginning in the 1950s at Cambridge where the first protein structures were determined in the laboratories of Max Perutz (hemoglobin, 1960) and John Kendrew (myoglobin, 1958). Michael's work was central in establishing and defining the field of structural biology, which amazingly has described the structures of a vast array of complex biological molecules and assemblies in atomic detail. Knowledge of three-dimensional biological structure has important biomedical significance including understanding the basis of health and disease at the molecular level, and facilitating the discovery of many drugs.

The Protein Data Bank: a historical perspective.

The Protein Data Bank began as a grassroots effort in 1971. It has grown from a small archive containing a dozen structures to a major international resource for structural biology containing more than 40000 entries. The interplay of science, technology and attitudes about data sharing have all played a role in the growth of this resource.

On wine, chirality and crystallography.

As the first centennial of X-ray diffraction is inevitably drawing closer, it is tempting to reflect on the impact that this fascinating discipline has had on natural sciences and how it has changed the world we live in. Also, next year is the 160th anniversary of the fateful April afternoon when Louis Pasteur separated D- from L-tartrate crystals, an event that many science historians recognize as the birth of stereochemistry, and the first step that the barely nascent field of crystallography took on the road to elucidate a fundamental phenomenon of chemistry and biology - chirality. Many great minds - Pasteur, Van 't Hoff, Fischer, Lord Kelvin, the Braggs, Astbury and Bijvoet, to mention just a few - contributed along the way. But one central inanimate character was there at all times - an inconspicuous somewhat obscure organic compound found in wine: tartaric acid. This is the story of its contribution to science.