Donald L. D. Caspar

Professor Emeritus of Biological Sciences
Ph.D. (1955) Yale
Member of the National Academy of Sciences

Institute of Molecular Biophysics     Tel: (850) 644-5522
Florida State University              Fax: (850) 644-7244
Tallahassee, FL 32306-4380  

Research Interests: Structural biology; x-ray, neutron and electron diffraction; protein plasticity.


How do protein molecules move to build complex structures, transmit and receive signals, activate substrates, do mechanical work and a myriad of other functions? The mechanics of protein movements are currently being explored in my laboratory by structural studies on insulin and other protein crystals under a variety of conditions and on tobacco mosaic virus and polymorphic assemblies of its coat protein.

The Caspar and Klug quasi-equivalence theory of icosahedral virus construction was based on the recognition that structural proteins are adaptable molecules that can self-assemble by bonding together in different ways within a highly ordered structure. Studies on the DNA containing tumor viruses have demonstrated that the molecular adaptability goes beyond the modest conformational adjustments anticipated in the quasi-equivalence theory; nevertheless essential bonding specificity is conserved in the contacts that tie the coat protein molecules together. As yet, there is no coherent picture of the switching mechanisms involved in the formation of any macromolecular biological assembly. Tobacco mosaic virus, which is the paradigm of a self-assembly structure, is the focus of renewed studies to investigate such structural switching. High resolution data on the coat protein structure in different assemblies is being obtained by diffraction methods with synchrotron radiation and by cryoelectron microscopy; and the self-organization of liquid crystalline virus specimens is being studied using methods of colloidal physics.

Tobacco mosaic virus particle and three views of the nucleating aggregate of its coat protein.

Crystals of well characterized small proteins such as insulin, diphtheria toxin repressor and interleukin 1β are serving as laboratories for investigating how atomic movements in proteins are correlated. Our studies on diffuse x-ray scattering demonstrate that the predominant component of the thermal fluctuations are correlated only over distances about the size of amino acid side chains. Correlations in the movements of protein atoms coordinating metal atoms are being explored by novel diffraction methods with synchrotron radiation. Protein plasticity is dependent of the restrained mobility of the surrounding solvent. We are characterizing the ordering of the fluctuating solvent structure and the role of water in mediating structural alterations by crystallographic methods as the pH, ionic composition and water activity of the solvent in cubic insulin crystals are varied.

The molecular movements involved in tobacco mosaic virus assembly have much in common with the movements the insulin molecule must undergo when it binds to its receptor. Piecing together a picture of how protein molecules in different systems can adapt their conformation in performing their biological function is the principal goal of this project. Realization of this goal is dependent on our methodological developments involving applications of diffuse x-ray scattering, high- and low-resolution x-ray and neutron crystallography, cryoelectron microscopy, fiber diffraction and computer graphics.

Original: February 5, 1998 by EF. | Updated: June 25, 2008 by TS.