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dc.contributor.advisorBarbara Imperiali.en_US
dc.contributor.authorAli, Mayssam H. (Mayssam Hani), 1976-en_US
dc.contributor.otherMassachusetts Institute of Technology. Dept. of Chemistry.en_US
dc.date.accessioned2005-06-02T18:27:08Z
dc.date.available2005-06-02T18:27:08Z
dc.date.copyright2004en_US
dc.date.issued2004en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/17737
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.en_US
dc.descriptionVita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractOligomeric mini-proteins, short peptides with protein-like features, constitute valuable minimal models for the study of oligomeric proteins. Oligomerization is a common feature of cellular proteins that may confer structural and functional advantages. Oligomerization is proposed to have arisen by several evolutionary pathways. The structural characterization of peptide 1, a stable oligomeric mini-protein previously developed in the Imperiali group, was undertaken by X-ray crystallography, as knowledge of the structure would enable the rational design of subsequent generations of BBA oligomers varying in packing and stoichiometry. The structure of peptide 1 could not be solved by direct methods, by molecular replacement with search models derived from the monomeric precursor, or by the introduction of heavy atoms. Two selenomethionine mutants having solution-phase properties comparable to the native were identified. The structures of these two peptides were independently solved via MAD phasing experiments, and the refined structures employed as search models for a molecular replacement solution of 1. The structures of the three peptides are homologous, and constitute the first reported structures of a mixed act/ oligomeric mini-protein. The X-ray crystal structures reveal that the oligomeric BBA motif has a domain-swapped architecture that supports a protein-like and water-exclusive core. The structures elucidate the unique role of unnatural amino acids in conferring native secondary structure in a short peptide sequence (21 residues per monomer).en_US
dc.description.abstract(cont.) Furthermore, the crystal structures reveal that the stoichiometry of the oligomer is tetrameric, rather than trimeric, as originally proposed. A tetrameric solution-phase stoichiometry for this mini-protein family was confirmed by rigorous analytical ultracentrifugation experiments. Heterooligomeric BBA peptides have been designed and characterized in collaboration with Christina M. Taylor and Professor Amy E. Keating of the MIT Biology Department. Acidic and basic residues were substituted along the inter-monomer interface and specific steric interactions were designed in order to disfavor homoassociation and favor heteroassociation. Heterotetramers comparable to peptide 1 in terms of structure and stoichiometry, and approaching the native homotetramer in terms of stability, have been characterized by a variety of biophysical techniques.en_US
dc.description.statementofresponsibilityby Mayssam H. Ali.en_US
dc.format.extent203 leavesen_US
dc.format.extent7351384 bytes
dc.format.extent7351191 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582
dc.subjectChemistry.en_US
dc.titleThe design and structural characterization of oligomeric beta beta alpha mini-proteinsen_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.identifier.oclc56481044en_US


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