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dc.contributor.authorMurray, John William
dc.date.accessioned2018-07-12T18:52:06Z
dc.date.available2018-07-12T18:52:06Z
dc.date.issued1997
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3420.;Advisors: John S. Condeelis.
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:9801914
dc.identifier.urihttps://hdl.handle.net/20.500.12202/3742
dc.description.abstractElongation factor 1 alpha (EF1{dollar}\alpha),{dollar} which binds aminoacyl-tRNA and ribosomes in a GTP dependent manner, is the most abundant component in protein synthesis. EF1{dollar}\alpha{dollar} also interacts with the cytoskeleton by binding and bundling actin filaments and microtubules. Purification of large quantities of EF1{dollar}\alpha{dollar} and actin from Dictyostelium allowed for the investigation of the activities of these two proteins in vitro, and this has lead us to propose a model whereby this translational factor and the actin cytoskeleton can coordinate their cellular functions.;EF1{dollar}\alpha{dollar} was shown to inhibit actin polymerization at molar ratios found in cytoplasm, while at higher molar ratios EF1{dollar}\alpha{dollar} also nucleates actin polymerization. The inhibition of actin polymerization by EF1{dollar}\alpha{dollar} was seen at both ends of the actin filament. Under these conditions EF1{dollar}\alpha{dollar} was shown to have relatively weak binding to G-actin. Quantitative analysis revealed that neither capping nor monomer sequestering mechanisms could account for the activity of EF1{dollar}\alpha{dollar} toward actin polymerization. A bundling model was developed which proposes that ends of actin filaments become buried and annealed during bundle formation causing a reduction in the rate of actin polymerization. The bundling model accounted for the activity of EF1{dollar}\alpha{dollar} toward actin polymerization and EF1{dollar}\alpha{dollar}-actin bundles were present under conditions where actin polymerization was inhibited. Observation of actin at steady state and during depolymerization also supported the bundling mechanism. Examination of whole cells indicated regions just beneath the cell cortex which contained EF1{dollar}\alpha{dollar} and actin as well as actin filaments in parallel arrays suggestive of EF1{dollar}\alpha{dollar}-actin bundles.;Investigation into the regulation of the EF1{dollar}\alpha{dollar}-actin interaction demonstrated that high pH and calcium-calmodulin dissolved EF1{dollar}\alpha{dollar}-actin bundles and released the effect of EF1{dollar}\alpha{dollar} on actin polymerization. The presence of aminoacyl-tRNA also dissolved GTP-EF1{dollar}\alpha{dollar}-actin bundles and also released the effect of EF1{dollar}\alpha{dollar} on actin polymerization. Thus, EF1{dollar}\alpha{dollar} and F-actin are predicted to form bundle-like structures beneath the cell cortex which are stabilized with respect to actin polymerization and depolymerization and which can be dissolved by intracellular signals such as pH, calcium-calmodulin, or by a local increase in the concentration of aminoacyl-tRNA. This system may facilitate the synthesis of polypeptides and cytosolic gelation-solution transitions.
dc.publisherProQuest Dissertations & Theses
dc.subjectCellular biology.
dc.subjectBiophysics.
dc.subjectBiochemistry.
dc.titleThe effect of elongation factor 1 alpha on actin polymer dynamics
dc.typeDissertation


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