Virus Structure and Assembly

Research Image

You have reached the Prevelige laboratory in the Department of Microbiology at the University of Alabama at Birmingham. The lab studies virus assembly using a wide variety of techniques. We are interested in the manner in which viral subunits specifically recognize one another and associate to from a closed viral capsid (as pictured above). One of the central questions is how otherwise identical protein subunits can alter their conformation to form hexavalent and pentavalent clusters (as pictured above) during the process of assembly. This phenomenon requires conformational plasticity in the subunit as well as control mechanisms to insure the proper positioning of the switched subunits on the growing capsid surface. Our general approach is to apply biophysical techniques to in vitro studies. Understanding the process of virus assembly is key to designing antivirals targeted at inhibition of assembly.

Experimental Systems and Approaches

The lab studies the assembly of two different viruses, the Salmonella typhimurium bacteriophage P22 and HIV. The P22 system affords the advantages of being a well defined system in which genetic manipulations are straightforward. Milligram quantities of structural proteins can be purified and studied in our in vitro assembly system. HIV is a technically more challenging system which affords the advantages of immediate medical relevance and providing a window in virus/host interactions. More detailed information on the research underway in the laboratory may be found by selecting the Research link. Individual projects are also described in the Members section.

The Structure and Assembly of dsDNA Bacteriophage

Bacteriophage assembly proceeds through the initial formation of a procapsid into which the DNA is packaged. The DNA is packaged through a portal located at one vertex. The “portal” protein forms a ring at the vertex and serves as one component of the ATP driven packaging motor. This talk illustrates the “finger trap” mechanism of portal function, and the structure of the nucleation complex responsible for portal incorporation.


Structure and Assembly of dsDNA Bacteriophage
ASV Annual Meeting
Madison, WI. July 2012

Research ImageMass Spectrometry of Macromolecular Complexes

Mass spectrometry has become a powerful technique in structural biology as witnessed by the 2002 Nobel prize in Chemistry. Hydrogen/deuterium exchange can provide information about the dynamics of macromolecular complexes as well as identifying subunit/subunit interfaces. This is particularly valuable when the sample of interest is poorly behaved (insoluble or polymorphous) or precious.We are using hydrogen/deuterium exchange to identify changes in intersubunit interfaces during viral morphogeneis, as well as to probe the dynamics of viral processes such as DNA packaging. In a parallel effort we are using chemical crosslinking and mass spec. analysis to obtain distance constraints which will then be used to position subunits of known three-dimensional structure in three dimensional space.

Video Research Seminar on Mass Spectrometry in Structural Biology
NIH September 2009.


Virus Based Nanotechnology

Viral capsids represent symmetrical nanoscale platforms that are amenable to both genetic and chemical manipulation. In collaboration with labs at the University of Alabama and Montana State University we are using bacteriophage P22 as a platform for photo-catalysis and nano-medicine. We have developed a variety of approaches to take advantage of the inherent symmetry of the capsid to pattern either semiconductor materials (photo-catalysis) or targeting peptides (nano-medicine) on the surface of the capsid. We have also developed a variety of approaches to load cargo such as TiO2, proteins, or nucleic acids into the interior of the particles.

Video Double Stranded DNA Bacteriophage as Nano-machines
Nanoscience Days
University of Jyväskylä
October 2009

Department of Microbiology
University of Alabama at Birmingham
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