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dc.contributor.authorGoldsmith, Sharon C.
dc.date.accessioned2018-07-12T19:00:45Z
dc.date.available2018-07-12T19:00:45Z
dc.date.issued2000
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 61-09, Section: B, page: 4697.;Advisors: Steven C. Almo.
dc.identifier.urihttps://yulib002.mc.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9985206
dc.identifier.urihttps://hdl.handle.net/20.500.12202/3907
dc.description.abstractThe actin cytoskeleton mediates a wide variety of biological processes ranging from cell motility and division to pathogen entry and infection. These diverse events are directed by the assembly of higher order macromolecular complexes of cytoskeletal proteins. The distinct atomic interactions contributing to protein-protein interfaces govern the specificities and functions of these complexes. It is therefore is crucial to obtain structural information for the actin binding proteins, in order to understand the mechanisms involved in cytoskeletal regulation. The crystal structure of the N-terminal actin binding domain from human fimbrin, an actin filament crosslinking protein, has been determined. Fimbrin is a representative member of a superfamily of actin binding proteins characterized by a conserved actin binding domain, therefore structural information obtained for fimbrin is applicable to other members of this family (including spectrin, alpha-actinin and dystrophin). The crystal structure of fimbrin provides the first high resolution structure of this actin binding domain and as a result, has led to the first atomic model of the fimbrin/F-actin complex. The atomic structure for the fimbrin/F-actin complex is a model, however, and the interface interactions that it proposes ultimately need to be investigated directly. As the fimbrin/F-actin complex is a structure not amenable to crystallographic analysis due to heterogeneity of the sample, it is evident that the development of novel experimental techniques designed to directly examine macromolecular interfaces is essential. Synchrotron X-ray footprinting has been applied to the investigation of protein complexes in solution, and developed as a method that probes the protein-protein interface. The gelsolin segment-1/actin complex has been employed as a model system for the development of X-ray protein footprinting. The gelsolin family of actin severing and capping proteins are composed of 3--6 repeats of a conserved 15 kD domain. The first of these domains in gelsolin, segment-1, binds to actin monomers and the crystal structure of this complex has elucidated specific amino acids in gelsolin segment-1 composing an actin binding helix. The actin-binding helix has been characterized by synchrotron footprinting. This result is the first X-ray footprint of a protein-protein complex and establishes X-ray protein footprinting as a widely applicable technique to probe macromolecular complexes.
dc.publisherProQuest Dissertations & Theses
dc.subjectBiochemistry.
dc.subjectCellular biology.
dc.subjectBiophysics.
dc.titleStructural analysis of cytoskeletal proteins by traditional and novel approaches
dc.typeDissertation


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