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dc.contributor.authorChowdhury, Pramit
dc.contributor.authorWang, Wei
dc.contributor.authorLavender, Stacey
dc.contributor.authorBunagan, Michelle R.
dc.contributor.authorKlemke, Jason W.
dc.contributor.authorTang, Jia
dc.contributor.authorSaven, Jeffrey G.
dc.contributor.authorCooperman, Barry S.
dc.contributor.authorGai, Feng
dc.identifier.citationChowdhury, P.; Wang, W.; Lavender, S.; Bunagan, M.R.; Klemke, J.W.; Tang, J.; Saven, J.G.; Cooperman, B.S.; Gai, F. "Fluorescence Correlation Spectroscopic Study of Serpin Depolymerization by Computationally Designed Peptides," Journal of Molecular Biology, 2007, 369, 462-473.en_US
dc.descriptionFile not available for download due to copyright restrictionsen_US
dc.description.abstractMembers of the serine proteinase inhibitor (serpin) family play important roles in the inflammatory and coagulation cascades. Interaction of a serpin with its target proteinase induces a large conformational change, resulting in insertion of its reactive center loop (RCL) into the main body of the protein as a new strand within β-sheet A. Intermolecular insertion of the RCL of one serpin molecule into the β-sheet A of another leads to polymerization, a widespread phenomenon associated with a general class of diseases known as serpinopathies. Small peptides are known to modulate the polymerization process by binding within β-sheet A. Here, we use fluorescence correlation spectroscopy (FCS) to probe the mechanism of peptide modulation of α1-antitrypsin (α1-AT) polymerization and depolymerization, and employ a statistical computationally-assisted design strategy (SCADS) to identify new tetrapeptides that modulate polymerization. Our results demonstrate that peptide-induced depolymerization takes place via a heterogeneous, multi-step process that begins with internal fragmentation of the polymer chain. One of the designed tetrapeptides is the most potent antitrypsin depolymerizer yet found.en_US
dc.subjectSerpin polymerizationen_US
dc.subjectComputer designen_US
dc.subjectFluorescence correlation spectroscopy (FCS)en_US
dc.subjectSerpin depolymerizationen_US
dc.titleFluorescence Correlation Spectroscopic Study of Serpin Depolymerization by Computationally Designed Peptidesen_US
prism.publicationNameJournal of Molecular Biologyen_US

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