THE DESIGN OF TWO PROTEINS THAT HAVE 100% SEQUENCE IDENTITY BUT ENCODE DIFFERENT FOLDS

dc.contributor.advisorBryan, Philipen_US
dc.contributor.authorMotabar, Danaen_US
dc.contributor.departmentBioengineeringen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2016-02-09T06:35:37Z
dc.date.available2016-02-09T06:35:37Z
dc.date.issued2015en_US
dc.description.abstractIt is well-established that proteins adopt specific three-dimensional structures. However, examples of proteins that can adopt more than one folded state have become increasingly more common. The objective of this thesis is to determine how three common, small folds are connected in sequence space. The folds this work focuses on are a 3-α-helix bundle, an α/β plait, and a 4β+α fold. Topological alignment and site-directed mutagenesis were used to develop engineered variants of the 3-α-helix bundle and the α/β plait folds that maintain their highly distinct native folds even though their sequences are 100% identical. CD and NMR data suggest that both proteins were stable and folded. This engineered fold switch demonstrates that the fold preference of a sequence is dependent upon stabilizing interactions within the context of the protein. These fold switching proteins have important implications in areas such as protein design, human disease, and structural biology.en_US
dc.identifierhttps://doi.org/10.13016/M20M8W
dc.identifier.urihttp://hdl.handle.net/1903/17377
dc.language.isoenen_US
dc.subject.pqcontrolledBiomedical engineeringen_US
dc.subject.pquncontrolledProtein Designen_US
dc.subject.pquncontrolledProtein Engineeringen_US
dc.subject.pquncontrolledProtein Evolutionen_US
dc.titleTHE DESIGN OF TWO PROTEINS THAT HAVE 100% SEQUENCE IDENTITY BUT ENCODE DIFFERENT FOLDSen_US
dc.typeThesisen_US

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