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DC Field | Value | Language |
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dc.contributor.advisor | Schwarzbauer, Jean E | - |
dc.contributor.author | Saunders, Jared | - |
dc.contributor.other | Molecular Biology Department | - |
dc.date.accessioned | 2019-11-05T16:50:14Z | - |
dc.date.available | 2019-11-05T16:50:14Z | - |
dc.date.issued | 2019 | - |
dc.identifier.uri | http://arks.princeton.edu/ark:/88435/dsp01hq37vr45g | - |
dc.description.abstract | The 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.iso | en | - |
dc.publisher | Princeton, NJ : Princeton University | - |
dc.relation.isformatof | The 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.subject | BMP-1 | - |
dc.subject | collagen | - |
dc.subject | extracellular matrix | - |
dc.subject | fibronectin | - |
dc.subject | heparin | - |
dc.subject | procollagen | - |
dc.subject.classification | Molecular biology | - |
dc.subject.classification | Cellular biology | - |
dc.title | FIBRONECTIN MATRIX AS A SCAFFOLD FOR PROCOLLAGEN PROTEASE BINDING AND COLLAGEN PROCESSING | - |
dc.type | Academic dissertations (Ph.D.) | - |
Appears in Collections: | Molecular Biology |
Files in This Item:
File | Description | Size | Format | |
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Saunders_princeton_0181D_13021.pdf | 48.52 MB | Adobe PDF | View/Download |
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