Ligand Binding Reveals a Role for Heme in Translationally-Controlled Tumor Protein Dimerization

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dc.contributor.authorLucas, Andrew T.en
dc.contributor.authorFu, Xiangpingen
dc.contributor.authorLiu, Jingjingen
dc.contributor.authorBrannon, Mary K.en
dc.contributor.authorYang, Jianhuaen
dc.contributor.authorCapelluto, Daniel G. S.en
dc.contributor.authorFinkielstein, Carla V.en
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2018-10-01T19:08:29Zen
dc.date.available2018-10-01T19:08:29Zen
dc.date.issued2014-11-14en
dc.description.abstractThe translationally-controlled tumor protein (TCTP) is a highly conserved, ubiquitously expressed, abundant protein that is broadly distributed among eukaryotes. Its biological function spans numerous cellular processes ranging from regulation of the cell cycle and microtubule stabilization to cell growth, transformation, and death processes. In this work, we propose a new function for TCTP as a “buffer protein” controlling cellular homeostasis. We demonstrate that binding of hemin to TCTP is mediated by a conserved His-containing motif (His76His77) followed by dimerization, an event that involves ligand-mediated conformational changes and that is necessary to trigger TCTP's cytokine-like activity. Mutation in both His residues to Ala prevents hemin from binding and abrogates oligomerization, suggesting that the ligand site localizes at the interface of the oligomer. Unlike heme, binding of Ca2+ ligand to TCTP does not alter its monomeric state; although, Ca2+ is able to destabilize an existing TCTP dimer created by hemin addition. In agreement with TCTP's proposed buffer function, ligand binding occurs at high concentration, allowing the “buffer” condition to be dissociated from TCTP's role as a component of signal transduction mechanisms.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0112823en
dc.identifier.eissn1932-6203en
dc.identifier.issue11en
dc.identifier.othere112823en
dc.identifier.pmid25396429en
dc.identifier.urihttp://hdl.handle.net/10919/85203en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleLigand Binding Reveals a Role for Heme in Translationally-Controlled Tumor Protein Dimerizationen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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