Franklin

A tale of two viruses with therapeutic potential : structural studies on CELO, an avian adenovirus, and the bacteriophage PRD1 / Lan Xu.

Author/Creator:
Xu, Lan.
Publication:
2002.
Format/Description:
Microformat
xiv, 234 p. : col. ill. ; 29 cm.
Local subjects:
Penn dissertations -- Chemistry.
Chemistry -- Penn dissertations.
Summary:
Viral assembly and disassembly are two major themes in the virus life cycle. Two virus systems will be focused on in this thesis as examples of the two themes. Chicken embryo lethal orphan (CELO) virus, an avian adenovirus, is the viral system used to study viral capsid organization and stabilization. CELO has potential as a gene transfer vector or vaccine carrier. It possesses a similar structure to human adenovirus, except that it has two fibers instead of one associated with each vertex, and lacks polypeptide IX, a cementing protein that stabilizes the capsid facet. These differences make its structural study intriguingly interesting. Milligrams of virus have been purified for virion crystallization trials and three-dimensional EM image reconstructions. Its major coat protein (942 residues, 106,709 Da), hexon, has also been purified and crystallized in space group P321 (a = 157.8 A, b = 157.8 A, c = 114.2 A, A = 90°, beta = 90°, gamma = 120°). With 45% sequence identity to human adenovirus type 5 hexon (951 residues), an initial model of the CELO hexon has been obtained by molecular replacement using the known structure of adenovirus type 5 hexon as the search model.
The second theme will be illustrated with a bacterial virus, bacteriophage PRD1. It is unusual, with an internal lipid membrane, but has striking resemblances to adenovirus that include its receptor-binding spike. Its vertex complex contains P2, a 590-residue monomer that binds to receptors on antibiotic-resistant strains of E. coli and so is the functional counterpart to the adenovirus fiber knob. P2 structures from two crystal forms, at 2.2 and 2.4 A resolution, reveal an elongated club-shaped molecule with a novel beta-propeller "head" showing pseudo sixfold symmetry. An extended loop forms a long "tail" containing a protruding proline-rich "fin", with another novel fold. The head and fin structures are well suited to recognition and attachment, which trigger the processes of vertex disassembly, membrane tube formation, and subsequent DNA injection.
Notes:
Supervisor: Roger M. Burnett.
Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 2002.
Includes bibliographical references.
Local notes:
University Microfilms order no.: 3073076.
Contributor:
Burnett, Roger M., advisor.
University of Pennsylvania.
ISBN:
9780493929651
OCLC:
244972898
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