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Skizzle: a Novel Streptococcus agalactiae-secreted Cofactor of Human Plasminogen Activation

dc.creatorWiles, Karen Godfrey
dc.description.abstractThe work in this thesis involves characterization of a novel Streptococcus agalactiae-secreted protein, skizzle, and its interactions with key proteins of the human fibrinolytic system. Skizzle binds human plasminogen (Pg) with high affinity and acts as a cofactor of Pg activation to form the clot-dissolving protease, plasmin. As a cofactor, skizzle uses two different mechanisms to enhance Pg activation by the endogenous Pg activators, urokinase and tissue-type plasminogen activator. Skizzle-enhanced Pg activation by urokinase is specific for the circulating, unmodified form, [Glu]Pg, and involves a skizzle-induced Pg conformational change to a more-easily activated conformation. Enhanced activation of both unmodified [Glu]Pg and modified [Lys]Pg by tissue-type plasminogen activator involves formation of a skizzle-containing ternary or quaternary complex with Pg and tissue-type plasminogen activator, resulting in enhanced Pg activation. To our knowledge, skizzle is the first S. agalactiae-secreted cofactor of human Pg activation. Skizzle has the potential to be a virulence factor in the pathogenesis of life-threatening S. agalactiae infections of newborns and immune-compromised adults.
dc.subjectstreptococcus agalactiae
dc.titleSkizzle: a Novel Streptococcus agalactiae-secreted Cofactor of Human Plasminogen Activation
dc.contributor.committeeMemberIngrid Verhammer
dc.contributor.committeeMemberDavid Gailani
dc.contributor.committeeMemberAndrzej Krezel
dc.contributor.committeeMemberEric Skaar
dc.contributor.committeeMemberPaul E. Bock (advisor)
dc.type.materialtext University
dc.contributor.committeeChairRichard Hoover

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