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dc.contributor.advisorVan Doren, Steven R., 1963-eng
dc.contributor.authorMarcink, Taraeng
dc.date.issued2018eng
dc.date.submitted2018 Springeng
dc.description.abstractMembrane type 1 matrix metalloproteinase (MT1-MMP) is essential to a myriad of extracellular activities including tumor cell migration and angiogenesis. At the cell surface, MT1-MMP is a major factor in the proteolysis of receptors, growth factors, and collagen. MT1-MMP extracellular domains bind the cell surface which can be influential in bringing these complexes together. This study uses new techniques to uncover the interactions between MT1-MMP and the cell surface. Described here is the development of techniques in protein and lipid preparations, NMR data acquisition, and structure determination by molecular dynamics simulations. Through these methods, the HPX domain was shown to bind nanodiscs by opposing tips of blade II and blade IV. The protruding part of these tips contain an EPGYPK sequence that are seen dipping into the membrane surface making contact with the lipid head groups. Blade IV membrane binding allows collagen to bind unhindered. Both blade II and blade IV membrane binding structures are shown to be favorable for homodimerization without disruption of the collagen binding site. The catalytic domain is shown to at least transiently bind membranes. This study then hypothesizes and discusses how these interactions impact both future peripheral protein membrane interaction studies and uncover similarities between the MMP family.eng
dc.description.bibrefIncludes bibliographical references.eng
dc.format.extentxvii, 190 pages : illustrationseng
dc.identifier.urihttps://hdl.handle.net/10355/68915
dc.identifier.urihttps://doi.org/10.32469/10355/68915eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.eng
dc.titleMembrane interactions with membrane type 1 matrix metalloproteinaseeng
dc.typeThesiseng
thesis.degree.disciplineBiochemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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