QUASI-EQUIVALENCE
Motion and Adaptability in Living Molecules
 Donald L. D. Caspar | On Friday and Saturday, January 10-11, 1997, the Structural Biology Program at Florida State University hosted a symposium entitled "Quasi-equivalence: Motion and Adaptability in Living Molecules". This symposium brought together experts from around the world to discuss the issues and fundamental principles that underlie the structure, assembly and action of macromolecules. The two days of scientific sessions at the Turnbull Center for Professional Development, in conjunction with the Institute of Molecular Biophysics, featured talks from 23 invited speakers and coincided with the 70th birthday of Donald L. D. Caspar, a co-founder of the concept of quasi-equivalence. |
Background
In 1962, Don Caspar and Aaron Klug introduced the concept of quasi-equivalence to
account for the arrangement of proteins on the surface of icosahedral virus
particles. This concept has played an important part in shaping the study
and understanding of viruses and other macromolecular assemblies for the
past 30 years. During that time the amount of information that we have
obtained about proteins has exploded, and the original concept, based mainly on
electron microscope studies, has been refined to take into account the
atomic resolution structure of viruses and other details of protein-protein
interactions that crystallography has elucidated. Thus, quasi-equivalence
continues to be an important component of the philosophical basis for how we
think about macromolecular assemblies. [MORE]
Speakers
By organizing this conference, we sought to bring together both the individuals
who were involved in the development of the concept from its origins, and
those who have generated high resolution information about macromolecular
assemblies and viruses over the past 30 years. This symposium was one of the few chances to bring together the originators
of the concepts with so many scientists who have contributed to its development.
It was a great opportunity to summarize the principles underlying our understanding
of macromolecular assemblies, and to define the questions we need to continue
asking about the movement and adaptability of macromolecules. The invited speakers included:
Tim Baker, Professor of Biological Sciences, Purdue University. He is revealing how viruses attach to cells and how they combine with antibodies that block infection by vividly reconstructing three-dimensional images from electron micrographs of frozen virus complexes and correlating atomic models with the electron images.
Barbara Brodsky, Professor of Biochemistry, Robert Wood Johnson Medical School of New Jersey. A leader in structure-function relationships in connective tissue, she is advancing our understanding of the role of collagen mutants in human disease.
Roger Burnett, Wistar Institute Professor, Department of Chemistry, University of Pennsylvania. Using X-ray crystallography, he determined the atomic structure of the adenovirus major coat protein, analyzed the complete virion by electron cryomicroscopy, and is extending structural studies of complex assemblies.
Michael Chapman, Assistant Professor of Chemistry, Institute of Molecular Biophysics, Florida State University. A versatile protein crystallographer, he is undertaking structural studies on viruses and enzymes with the goal of re-engineering assemblies for clinical applications.
James Clarage, Assistant Professor, Institute for Biosciences, Rice University. A computational biologist and freelance electronic artist, he has combined interpretation of diffuse X-ray scattering with molecular dynamics calculations to demonstrate the chaotic but locally correlated motions of biomolecules.
Carolyn Cohen, Professor of Biology, Rosenstiel Basic Medical Research Center, Brandeis University. Member of the National Academy of Sciences. She has pioneered the decipherment of the atomic structure of fibrous proteins and their functional assemblies in muscle, tendon, and blood clots, and is now elucidating the molecular regulation and mechanics of muscle contraction.
David DeRosier, Professor of Biology, Rosenstiel Basic Medical Research Center, Brandeis University. Inventor with Aaron Klug of the method of three-dimensional image reconstruction from electron micrographs, he is visualizing the bacterial rotary flagellar machinery and actin-containing cytoskeletal components of eukaryotic cells using advanced methods of image analysis.
David Eisenberg, Professor of Chemistry, Laboratory of Structural Biology and Molecular Medicine, University of California at Los Angeles. Member of the National Academy of Sciences. How the three-dimensional structure of proteins is determined by their amino acid sequence is a prime focus of his comprehensive research involving computational analysis, protein design and X-ray crystallography of enzyme complexes and model structures.
Steve Harrison, Professor of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Harvard University. Member of the National Academy of Sciences. The initiator of atomic resolution virus crystallography, he is leading the way in determining the detailed structure of more and more complex virus particles and visualizing the interactions of regulatory protein complexes with DNA.
Kenneth Holmes, Director, Max-Plank-Institut für Medizinishe Forschung, Abteilung für Biophysik, Heidelberg. Fellow of the Royal Society. He began the use of synchrotron radiation in structural biology, and is illuminating the structure of actin filaments in muscle and their role in the contractile process.
John Johnson, Member, The Scripps Research Institute, La Jolla, CA. Based on his productive atomic resolution studies of virus structures, he is charac-terizing the formation of quasi-equivalent viral capsids and polymorphic assemblies using the tools of molecular biology, electron microscopy, computational chemistry and X-ray crystallography.
Johnathan King, Professor of Molecular Biology, Massachusetts Institute of Technology. Innovator in molecular virology, he has applied his insights into the control of virus assembly to develop new approaches to the protein folding problem and molecular diseases.
Sir Aaron Klug, President of the Royal Society, Former Director of the MRC Laboratory of Molecular Biology, Cambridge. Awarded the Nobel Prize for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes, he has profoundly influenced the course of structural biology from its early development to its bright future.
Robert Langridge, Professor Emeritus, Departments of Pharmaceutical Chemistry and Biochemistry/Biophysics, University of California at San Francisco, and Visiting Professor of Biochemistry and Biophysics, Oregon State University. Member of the Institute of Medicine. First to use a digital computer to analyze DNA structures, he became a pioneer in molecular graphics and established the influential Computer Graphics Laboratory as a National Research Resource, first at Princeton and now at San Francisco.
Vittorio Luzzati, Former Head, Centre de Genetique Moleculaire, CNRS, Gif sur Yvette, France. Author early in his career of one of the most-cited papers in protein crystallography which displayed his mathematical ingenuity, he went on to analyze by experiment and modeling the complexity of lipid-water systems and membrane structures.
Lee Makowski, Professor of Biological Sciences and of Chemistry, Director of the Institute of Molecular Biophysics, Florida State University. A leader in the structural analysis of non-crystalline macromolecular assemblies, he is guiding the development of a broadly-based program in structural biology at FSU.
Eckhart Mandelkow, Director, Max-Plank, Gesellschaft Unit of Structural Molecular Biology, Hamburg. How microtubules assemble and mediate intercellular transport, and how the microtubule associated protein tau is involved in forming pathological aggregates in Alzheimer's disease has been illuminated by his biophysical and biochemical studies.
Keiichi Namba, Group Leader, International Institute for Advanced Research, Masushita Electric Industrial Co., Ltd., Seika, Japan. Having solved with Gerald Stubbs the structure of tobacco mosaic virus, he then catalyzed the establishment of a new center for structural biology with industry support where he is exploring the molecular machinery of bacterial motility.
Adrian Parsegian, Chief, Laboratory of Structural Biology, Computer Research and Technology Division, National Institutes of Health. Biophysical proponent and pioneer, he has opened up novel approaches to measure the forces between interacting macromolecular structures that are involved in higher levels of membrane, nucleic acid, tendon and cytoskeletal organization.
Clarence E. Schutt, Professor of Chemistry, Princeton University. An imaginative intellect, he has determined the variable atomic structure of actin complexed with profilin, and has formulated a provocative model for the action of actin in muscle contraction.
Robert Stroud, Professor of Biochemistry and Biophysics, University of California at San Francisco. He is resourcefully applying methods of protein crystallography to explore the regulation of enzyme action, drug design and mechanisms of molecular recognition and cellular signaling.
Gerald Stubbs, Professor of Molecular Biology, Vanderbilt University. He developed ways to analyze macromolecular fiber diffraction data which were used with Keiichi Namba to solve the structure of tobacco mosaic virus, and his further studies on helical viruses are being related to molecular genetics results to explain assembly mechanisms.
Kenneth Taylor, Professor of Biological Sciences, Florida State University. Pioneered the field of cryoelectron microscopy of macromolecules and the 3D imaging of the contractile apparatus of muscle in different states, he is now developing methods for structure determination of muscle protein by electron crystallography of 2D arrays.
Don Wiley, Professor of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Harvard University. Member of the National Academy of Sciences. The Lasker Award recognized his insightful structural analyses of proteins involved in antigen recognition, which are defining how the immune system distinguishes "self" from "non-self"; his demonstration of the dramatic switching of the influenza surface glycoprotein indicates how the virus invades a cell.
Robley Williams, Jr.,
Professor of Molecular Biology, Vanderbilt University.
His painstaking work on the structure and dynamics of microtubule
assembly and disassembly has led to striking images of the action
of these critical structures.
Proceedings
FRIDAY, 10 JANUARY 1997
The Biophysical Journal has published a special section in the January 1998 issue containing
papers presented at the Quasi-equivalence Symposium as well as current research in the field and tributes to Dr. Caspar - the man and his research - by Carolyn Cohen and Lee Makowski. Following is a list of those publications as well as other recent papers pertaining to quasi-equivalence.
Caspar, D. L. D. and Fontano, E. (1996) "Five-fold symmetry in crystalline quasicrystal lattices." Proc. Nat. Acad. Sci. USA 93:14271-14278.
Luzzati, V., Mateu, L., Vonasek, E., Borgo, M. and Marquez, G. (1998) "Nerve Excitability and Lipid Chain Conformation: An X-ray Scattering and Electrophysiological Approach." In preparation.