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dc.contributor.authorAlajlouni, Rubaen_US
dc.date.accessioned2017-04-04T19:50:44Z
dc.date.available2017-04-04T19:50:44Z
dc.date.issued2011-04-21en_US
dc.identifier.otheretd-05032011-071428en_US
dc.identifier.urihttp://hdl.handle.net/10919/76980
dc.description.abstractDisabled-2 (Dab2) is an adapter protein that interacts with cell membranes and it is involved in several biological processes including endocytosis and platelet aggregation. During endocytosis, the Dab2 phosphotyrosine-binding (PTB) domain mediates protein binding to phosphatidylinositol 4,5-bisphosphate (PIP2) at the inner leaflet of the plasma membrane and helps co-localization with clathrin coats. Dab2, released from platelet alpha granules, inhibits platelet aggregation by binding to the °IIb? integrin receptor on the platelet surface through an Arg-Gly-Asp (RGD) motif located within the PTB domain. Alternatively, Dab2 binds sulfatides on the platelets surface, and this binding partition Dab2 in two pools (sulfatide and integrin receptor-bound states), but the biological consequences of lipid binding remain unclear. Dab2 binds sulfatides through two basic motifs located on its N-terminal region including the PTB domain (N-PTB). We have characterized the binding of Dab2 to micelles, which are widely used to mimic biological membranes. These micellar interactions were studied in the absence and presence of Dab2 lipid ligands, sulfatides and PIP2. By applying multiple biochemical, biophysical, and structural techniques, we found that whereas Dab2 N-PTB binding to PIP2 stabilized the protein but did not contribute to the penetration of the protein into micelles, sulfatides induced conformational changes and facilitated penetration of Dab2 N-PTB into micelles. This is in agreement with previous observation that sulfatides, but not PIP2, protect Dab2 N-PTB from thrombin cleavage. By studying the mechanism by which Dab2 targets membranes, we will have the opportunity to manipulate its function in different lipid-dependent biological processes.
dc.language.isoen_USen_US
dc.publisherVirginia Techen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subject5-bisphosphateen_US
dc.subjectCircular Dichroismen_US
dc.subjectMicellesen_US
dc.subjectSulfatideen_US
dc.subjectTryptophan Fluorescenceen_US
dc.subjectDisabled-2en_US
dc.subjectNuclear Magnetic Resonanceen_US
dc.subjectPhosphatidylinositol 4en_US
dc.subjectAcrylamide quenchingen_US
dc.titleMembrane binding properties of Disabled-2en_US
dc.typeThesisen_US
dc.contributor.departmentBiological Sciencesen_US
dc.description.degreeMaster of Scienceen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiological Sciencesen_US
dc.contributor.committeechairCapelluto, Daniel G. S.en_US
dc.contributor.committeememberLawrence, Christopher B.en_US
dc.contributor.committeememberSible, Jill C.en_US
dc.type.dcmitypeTexten_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05032011-071428/en_US
dc.date.sdate2011-05-03en_US
dc.date.rdate2016-09-27
dc.date.adate2011-05-10en_US


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