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Gerald Stubbs

Structural Studies of Filamentous Viruses

Gerald Stubbs, Emeritus

Knowing the detailed three-dimensional structure of biological macromolecules and assemblies is essential to an understanding of their functions, including control of their activity. We are studying the molecular structure of filamentous biological assemblies, including filamentous plant viruses, prions and other amyloids. We use x-ray fiber diffraction, cryo-electron microscopy, and other biophysical methods of structure determination.

We determined the structure of tobacco mosaic virus at 2.9 A resolution in the 1980s. This enabled us to understand the mechanism of control of assembly of this virus. Through collaborations with molecular geneticists, we have designed and studied mutations of the virus that affect viral assembly, disassembly, transport and host defense mechanisms. We are currently studying several viruses related to TMV, as well as a number of more flexible viruses, particularly those in the potexvirus, potyvirus, and closterovirus groups. We have recently published evidence that flexible filamentous plant viruses all share common structural features; these data have important implications both for basic understanding of viral structure and evolution, and for agriculture and biotechnology.

Prions are responsible for such diseases as Creutzfeldt-Jacob disease and “mad cow disease”; they are infectious amyloids, misfolded proteins with no nucleic acid component. Amyloids are implicated in many diseases, including Alzheimer’s and Parkinson’s diseases. We have obtained the first diffraction data from mammalian prions, and we are developing structural models for these and several other amyloids.

We are also interested in developing new methods in fiber diffraction, particularly for use in disordered filamentous assemblies.