TWO CASE STUDIES OF PROTEIN FOLD EVOLUTION: BACTERIOPHAGE CRO PROTEINS AND INSECT SALIVARY LIPOCALINS

Persistent Link:
http://hdl.handle.net/10150/194488
Title:
TWO CASE STUDIES OF PROTEIN FOLD EVOLUTION: BACTERIOPHAGE CRO PROTEINS AND INSECT SALIVARY LIPOCALINS
Author:
Roessler, Christian George
Issue Date:
2010
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:
Natural proteins can evolve new three-dimensional structures through mutations in their amino acid sequence. For protein families that exhibit such structural diversity, a major challenge is to understand the scope and nature of structure variation and its relationship to sequence evolution. The Cordes laboratory has begun using transitive homology-based methods to identify, target and structurally characterize natural sequences intermediate between pairs of proteins with distant sequence similarity and different structures. As a proof of principle, this dissertation describes structural studies of two proteins in different families as separate case studies, one involving secondary structure evolution and the other involving topological rearrangement. In the first case, crystallography was applied to solve the structure of a sequence intermediate identified through transitive homology analysis of the Cro transcription regulator family. Comparison with another member resulted in finding two proteins with significant sequence similarity yet different secondary structure compositions and folds. In the second case, transitive homology analysis was applied to look at two members of the insect salivary lipocalins, one with the canonical sequential all-antiparallel β-barrel topology, and another with a unique strand-swapped topology. Three sequence intermediate members were found that each have direct sequence similarity to both topologically distinct relatives. Targeting these sequence intermediate members for structural characterization by NMR led to assignment of the canonical lipocalin topology for one intermediate. The results from these two cases indicate that structurally diverse families may contain members with similar sequences but different folds. As such, transitive homology mapping offers a method to identify and target those members for structural characterization.
Type:
text; Electronic Dissertation
Keywords:
Cro; Evolution; Fold; Lipocalin; Protein; Structure
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Biochemistry; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Cordes, Matthew H. J.
Committee Chair:
Cordes, Matthew H. J.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleTWO CASE STUDIES OF PROTEIN FOLD EVOLUTION: BACTERIOPHAGE CRO PROTEINS AND INSECT SALIVARY LIPOCALINSen_US
dc.creatorRoessler, Christian Georgeen_US
dc.contributor.authorRoessler, Christian Georgeen_US
dc.date.issued2010en_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.abstractNatural proteins can evolve new three-dimensional structures through mutations in their amino acid sequence. For protein families that exhibit such structural diversity, a major challenge is to understand the scope and nature of structure variation and its relationship to sequence evolution. The Cordes laboratory has begun using transitive homology-based methods to identify, target and structurally characterize natural sequences intermediate between pairs of proteins with distant sequence similarity and different structures. As a proof of principle, this dissertation describes structural studies of two proteins in different families as separate case studies, one involving secondary structure evolution and the other involving topological rearrangement. In the first case, crystallography was applied to solve the structure of a sequence intermediate identified through transitive homology analysis of the Cro transcription regulator family. Comparison with another member resulted in finding two proteins with significant sequence similarity yet different secondary structure compositions and folds. In the second case, transitive homology analysis was applied to look at two members of the insect salivary lipocalins, one with the canonical sequential all-antiparallel β-barrel topology, and another with a unique strand-swapped topology. Three sequence intermediate members were found that each have direct sequence similarity to both topologically distinct relatives. Targeting these sequence intermediate members for structural characterization by NMR led to assignment of the canonical lipocalin topology for one intermediate. The results from these two cases indicate that structurally diverse families may contain members with similar sequences but different folds. As such, transitive homology mapping offers a method to identify and target those members for structural characterization.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectCroen_US
dc.subjectEvolutionen_US
dc.subjectFolden_US
dc.subjectLipocalinen_US
dc.subjectProteinen_US
dc.subjectStructureen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineBiochemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorCordes, Matthew H. J.en_US
dc.contributor.chairCordes, Matthew H. J.en_US
dc.contributor.committeememberGhosh, Indraneelen_US
dc.contributor.committeememberMcEvoy, Meganen_US
dc.contributor.committeememberMontfort, Williamen_US
dc.identifier.proquest11307en_US
dc.identifier.oclc752261153en_US
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