Persistent Link:
http://hdl.handle.net/10150/195146
Title:
The Protein Binding Potential of C2H2 Zinc Finger Domains
Author:
Brayer, Kathryn Jo
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Cys2-His2 (C2H2) zinc finger domains were originally identified as DNA binding domains, and uncharacterized domains are typically assumed to bind DNA. However, a growing body of evidence suggests an important and widespread role for these domains in protein binding. Over 100 C2H2 zinc finger-protein interactions have been described. This study uses common bioinformatics tools to identify sequence features that predict a DNA- or protein-binding function. Several issues, including uncertainties about the full functional capabilities of the zinc fingers, complicated these efforts. Therefore, an unbiased approach which directly examined the potential for zinc fingers to facilitate DNA or protein interactions was used to determine the full functional capabilities of the C2H2 domains in two model proteins, human OLF-1/EBF associated zinc finger (OAZ) protein and Zif268. OAZ contains 30 zinc fingers in six clusters, some of which have been previously indicated in DNA or protein interactions. Zif268 is a well-known DNA binding protein with three C2H2 domains. DNA binding was assessed using a target site selection (CAST) assay, and protein binding was assessed using a yeast two-hybrid assay. Results indicate that clusters known to bind DNA could facilitate specific protein interactions, but clusters known to bind protein did not facilitate specific DNA interactions, indicating that DNA binding is a more restricted function of zinc fingers than has previously been recognized. These results also suggest that the role of C2H2 zinc finger domains in protein interactions has probably been underestimated. The implication of these findings for the prediction of zinc finger function is discussed.
Type:
text; Electronic Dissertation
Keywords:
transcription factors; protein-DNA interactions; protein-protien interactions; protein chemistry; structural biology; functional annotations
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Pharmacology & Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Segal, David J.; Vaillancourt, Richard R.
Committee Chair:
Segal, David J.; Vaillancourt, Richard R.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleThe Protein Binding Potential of C2H2 Zinc Finger Domainsen_US
dc.creatorBrayer, Kathryn Joen_US
dc.contributor.authorBrayer, Kathryn Joen_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractCys2-His2 (C2H2) zinc finger domains were originally identified as DNA binding domains, and uncharacterized domains are typically assumed to bind DNA. However, a growing body of evidence suggests an important and widespread role for these domains in protein binding. Over 100 C2H2 zinc finger-protein interactions have been described. This study uses common bioinformatics tools to identify sequence features that predict a DNA- or protein-binding function. Several issues, including uncertainties about the full functional capabilities of the zinc fingers, complicated these efforts. Therefore, an unbiased approach which directly examined the potential for zinc fingers to facilitate DNA or protein interactions was used to determine the full functional capabilities of the C2H2 domains in two model proteins, human OLF-1/EBF associated zinc finger (OAZ) protein and Zif268. OAZ contains 30 zinc fingers in six clusters, some of which have been previously indicated in DNA or protein interactions. Zif268 is a well-known DNA binding protein with three C2H2 domains. DNA binding was assessed using a target site selection (CAST) assay, and protein binding was assessed using a yeast two-hybrid assay. Results indicate that clusters known to bind DNA could facilitate specific protein interactions, but clusters known to bind protein did not facilitate specific DNA interactions, indicating that DNA binding is a more restricted function of zinc fingers than has previously been recognized. These results also suggest that the role of C2H2 zinc finger domains in protein interactions has probably been underestimated. The implication of these findings for the prediction of zinc finger function is discussed.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjecttranscription factorsen_US
dc.subjectprotein-DNA interactionsen_US
dc.subjectprotein-protien interactionsen_US
dc.subjectprotein chemistryen_US
dc.subjectstructural biologyen_US
dc.subjectfunctional annotationsen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology & Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorSegal, David J.en_US
dc.contributor.advisorVaillancourt, Richard R.en_US
dc.contributor.chairSegal, David J.en_US
dc.contributor.chairVaillancourt, Richard R.en_US
dc.contributor.committeememberRegan, Johnen_US
dc.contributor.committeememberCordes, Matten_US
dc.contributor.committeememberHorton, Nancyen_US
dc.identifier.proquest2570en_US
dc.identifier.oclc659748503en_US
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