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Role of basic and hydrophobic residues in the poliovirus polymerase elongation complex and the structure of a coxsackievirus polymerase elongation complex

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dc.contributor.authorKortus, Matt, author
dc.contributor.authorPeersen, Olve, advisor
dc.contributor.authorHo, P. Shing, committee member
dc.contributor.authorSuchman, Erica, committee member
dc.date.accessioned2007-01-03T05:36:18Z
dc.date.available2007-01-03T05:36:18Z
dc.date.issued2011
dc.description.abstractPicornaviruses encode for and require a viral RNA-dependent RNA polymerase (RdRP) for genome replication. This enzyme synthesizes negative-sense RNA from the infecting positive sense genome producing a replicative intermediate. The negative sense RNA then serves as a template for synthesis of additional positive-sense RNA. To efficiently replicate the genome, RdRPs must form a stable and processive elongation complex (EC) by binding RNA, incorporating the first templating nucleotide, and undergoing a necessary conformational. Upon completion of these steps that comprise initiation, the newly formed EC is capable of rapidly replicating the viral genome. The work presented in this thesis 1) investigates the role that several basic and hydrophobic residues serve in forming and maintaining the poliovirus (PV) EC and 2) presents the crystal structure of a coxsackievirus (CV) EC. To determine the role of that several arginines, lysines, and tyrosines play in the PV polymerase, we assessed whether mutations to these residues affect initiation, elongation, or stability of the EC. The data indicates the basic residues within the fingers domain of the PV polymerase have a major role in binding RNA. In addition, data shows two tyrosine residues in particular are critical for formation and maintenance of the EC. Overall, the data provides evidence the fingers domain interacts with the template RNA in a manner not captured by crystal structures. Finally, we have solved the structure of a CVEC stalled after incorporation of four nucleotides. The CVEC structure closely matches the previously solved PVEC structure. In addition, one crystal form produced an elongation complex trapped in a translocation intermediate state.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierKortus_colostate_0053N_10747.pdf
dc.identifier.urihttp://hdl.handle.net/10217/79449
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectcoxsackievirus
dc.subjectpolymerase
dc.subjectpoliovirus
dc.subjectcrystallography
dc.titleRole of basic and hydrophobic residues in the poliovirus polymerase elongation complex and the structure of a coxsackievirus polymerase elongation complex
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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