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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp01hq37vr45g
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dc.contributor.advisorSchwarzbauer, Jean E-
dc.contributor.authorSaunders, Jared-
dc.contributor.otherMolecular Biology Department-
dc.date.accessioned2019-11-05T16:50:14Z-
dc.date.available2019-11-05T16:50:14Z-
dc.date.issued2019-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/dsp01hq37vr45g-
dc.description.abstractThe extracellular matrix (ECM) proteins fibronectin (FN) and type I collagen (collagen I) are co-distributed in many tissues and collagens have been shown to depend on a FN matrix for fibrillogenesis. Despite extensive understanding of supramolecular collagen fiber structure and matrix deposition, the molecular interactions of the proteolytic processing of collagen’s biosynthetic precursor, type I procollagen (procollagen I), have not been elucidated, in particular the role of FN matrix in that process. Microscopic analysis of a fibroblast ECM showed co-localization of procollagen I with FN fibrils and inhibition of FN matrix assembly led to a significant reduction of proteolytic cleavage of procollagen to initiate fibril formation, and a concurrent enrichment of collagens containing one or both propeptides. We examined the role of FN matrix in procollagen processing by the C-propeptide proteinase BMP-1. We found that BMP-1, like procollagen, co-localizes with FN fibrils in the matrix microenvironment. Binding studies with FN fragments identified a binding site in FN’s primary heparin binding domain. In solution, BMP-1-FN interactions and BMP-1 cleavage of procollagen I were both enhanced by the presence of heparin suggesting a role for heparin in complex formation during proteolysis. Indeed, addition of heparin enhanced the rate of procollagen cleavage by matrix-bound BMP-1. Our results show that matrix localization of this proteinase facilitates the initiation of collagen assembly and suggest a model in which FN matrix and associated heparan sulfate act as a scaffold to organize enzyme and substrate for procollagen processing.-
dc.language.isoen-
dc.publisherPrinceton, NJ : Princeton University-
dc.relation.isformatofThe Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: <a href=http://catalog.princeton.edu> catalog.princeton.edu </a>-
dc.subjectBMP-1-
dc.subjectcollagen-
dc.subjectextracellular matrix-
dc.subjectfibronectin-
dc.subjectheparin-
dc.subjectprocollagen-
dc.subject.classificationMolecular biology-
dc.subject.classificationCellular biology-
dc.titleFIBRONECTIN MATRIX AS A SCAFFOLD FOR PROCOLLAGEN PROTEASE BINDING AND COLLAGEN PROCESSING-
dc.typeAcademic dissertations (Ph.D.)-
Appears in Collections:Molecular Biology

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