{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10315"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10315","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Structural and Molecular Mechanisms of Centrosome Assembly and Strength","abstract":"The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular interactions that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly. Multimerization of SPD-5 is driven by interactions between multiple dispersed coiled-coil domains. Structural analyses of a phosphorylated region (PReM) in SPD-5 revealed a helical hairpin that dimerizes to form a tetrameric coiled-coil. Mutations within this structure and other interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces, revealing that PCM assembly and strength are interdependent. We propose that PCM size and strength emerge from specific, multivalent coiled-coil interactions between SPD-5 proteins.","abstract_html":"The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular interactions that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly. Multimerization of SPD-5 is driven by interactions between multiple dispersed coiled-coil domains. Structural analyses of a phosphorylated region (PReM) in SPD-5 revealed a helical hairpin that dimerizes to form a tetrameric coiled-coil. Mutations within this structure and other interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces, revealing that PCM assembly and strength are interdependent. We propose that PCM size and strength emerge from specific, multivalent coiled-coil interactions between SPD-5 proteins.","abstract_has_math":false,"creators":["Rios, Manolo Uriel"],"institution":"UT Southwestern Medical Center","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Cell and Molecular Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Doubrovinski, Konstantin"],"committee_chairs":[],"committee_members":["Rosen, Michael K.","Woodruff, Jeffrey B.","Seemann, Joachim"],"year":2024,"date_issued":"2024-05","date_published":"2024-05","updated_at":"2026-08-21T16:50:23Z","subjects":["Cell Cycle Proteins","Centrosome","Polo-Like Kinase 1","Caenorhabditis elegans"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1438579295"],"render_values":[{"text":"1438579295","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10315","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"source_record":{"url":"https://utswmed-ir.tdl.org/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Autswmed-ir.tdl.org%3A2152.5%2F10315","prefix":"dim"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Doubrovinski, Konstantin","Rosen, Michael K.","Woodruff, Jeffrey B.","Seemann, Joachim"]},{"key":"dc:contributor.advisor","label":"Advisor","values":["Doubrovinski, Konstantin"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Rosen, Michael K.","Woodruff, Jeffrey B.","Seemann, Joachim"]},{"key":"dc:creator","label":"Author","values":["Rios, Manolo Uriel"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-06-07T19:15:41Z","2024-05","May 2024"]},{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-06-07T19:15:41Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-06-07T19:15:41Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Molecular Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["UT Southwestern Medical Center"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cell Cycle Proteins","Centrosome","Polo-Like Kinase 1","Caenorhabditis elegans"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10315","1438579295"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.5/10315"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular interactions that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly. Multimerization of SPD-5 is driven by interactions between multiple dispersed coiled-coil domains. Structural analyses of a phosphorylated region (PReM) in SPD-5 revealed a helical hairpin that dimerizes to form a tetrameric coiled-coil. Mutations within this structure and other interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces, revealing that PCM assembly and strength are interdependent. We propose that PCM size and strength emerge from specific, multivalent coiled-coil interactions between SPD-5 proteins."]},{"key":"dc:description.abstract","label":"Abstract","values":["The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular interactions that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly. Multimerization of SPD-5 is driven by interactions between multiple dispersed coiled-coil domains. Structural analyses of a phosphorylated region (PReM) in SPD-5 revealed a helical hairpin that dimerizes to form a tetrameric coiled-coil. Mutations within this structure and other interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces, revealing that PCM assembly and strength are interdependent. We propose that PCM size and strength emerge from specific, multivalent coiled-coil interactions between SPD-5 proteins."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Structural and Molecular Mechanisms of Centrosome Assembly and Strength"]}]}],"canonical_facts":{"dc:contributor":["Doubrovinski, Konstantin","Rosen, Michael K.","Woodruff, Jeffrey B.","Seemann, Joachim"],"dc:contributor.advisor":["Doubrovinski, Konstantin"],"dc:contributor.committeemember":["Rosen, Michael K.","Woodruff, Jeffrey B.","Seemann, Joachim"],"dc:creator":["Rios, Manolo Uriel"],"dc:date":["2024-06-07T19:15:41Z","2024-05","May 2024"],"dc:date.accessioned":["2024-06-07T19:15:41Z"],"dc:date.available":["2024-06-07T19:15:41Z"],"dc:date.issued":["2024-05"],"dc:description":["The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular interactions that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly. Multimerization of SPD-5 is driven by interactions between multiple dispersed coiled-coil domains. Structural analyses of a phosphorylated region (PReM) in SPD-5 revealed a helical hairpin that dimerizes to form a tetrameric coiled-coil. Mutations within this structure and other interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces, revealing that PCM assembly and strength are interdependent. We propose that PCM size and strength emerge from specific, multivalent coiled-coil interactions between SPD-5 proteins."],"dc:description.abstract":["The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. To answer such question, we use cross-linking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular interactions that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly. Multimerization of SPD-5 is driven by interactions between multiple dispersed coiled-coil domains. Structural analyses of a phosphorylated region (PReM) in SPD-5 revealed a helical hairpin that dimerizes to form a tetrameric coiled-coil. Mutations within this structure and other interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces, revealing that PCM assembly and strength are interdependent. We propose that PCM size and strength emerge from specific, multivalent coiled-coil interactions between SPD-5 proteins."],"dc:format":["application/pdf"],"dc:format.mimetype":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10315","1438579295"],"dc:identifier.uri":["https://hdl.handle.net/2152.5/10315"],"dc:language":["en"],"dc:language.iso":["en"],"dc:subject":["Cell Cycle Proteins","Centrosome","Polo-Like Kinase 1","Caenorhabditis elegans"],"dc:title":["Structural and Molecular Mechanisms of Centrosome Assembly and Strength"],"dc:type":["Thesis","text"],"thesis:degree_discipline":["Cell and Molecular Biology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["UT Southwestern Medical Center"]},"updated_at":"2026-08-21T16:50:23Z"}