| Probing nanosecond motions of plasminogen activator inhibitor-1 by time-resolved fluorescence anisotropy. | |
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MedLine Citation:
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PMID: 19668868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin (serine protease inhibitor) superfamily. Like most serpins, the inhibitory function of PAI-1 relies on a flexible reactive centre loop (RCL) undertaking a striking conformational transition. We have investigated the conformational dynamics of the RCL of PAI-1 by time-resolved fluorescence anisotropy. A heterogeneous population model with three rotational correlation times has been employed to account for the "dip and rise" observed in fluorescence anisotropy decay curves. The RCL becomes almost fully solvent exposed and exhibits faster rotation when PAI-1 interacts with a RCL-mimicking octapeptide which blocks the loop insertion pathway, indicating that the RCL is well displaced from the protein surface; while the binding of Somatomedin B (SMB) domain of vitronectin, only induces small changes in the RCL. Comparison of the fluorescence lifetime and anisotropy decay of the wild-type PAI-1 with that of the stabilised mutant suggests that there would be no major structural differences between them. Our results indicate that in a native serpin, the P14 residue of the hinge region can flip in and out of the central beta-sheet A more readily than previously thought, which is likely an inherent property for serpins' protease inhibitory function. |
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Authors:
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Chin Wing Ko; Zhenquan Wei; Richard J Marsh; Daven A Armoogum; Nick Nicolaou; Angus J Bain; Aiwu Zhou; Liming Ying |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-07 |
Journal Detail:
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Title: Molecular bioSystems Volume: 5 ISSN: 1742-2051 ISO Abbreviation: Mol Biosyst Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-11 Completed Date: 2009-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101251620 Medline TA: Mol Biosyst Country: England |
Other Details:
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Languages: eng Pagination: 1025-31 Citation Subset: IM |
Affiliation:
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Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UKSW7 2AZ. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Fluorescence Polarization
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methods* Fluorescent Dyes / chemistry Models, Molecular Nanotechnology / methods* Naphthalenesulfonates / chemistry Plasminogen Activator Inhibitor 1 / chemistry*, metabolism Protein Conformation Protein Structure, Tertiary Recombinant Proteins Somatomedins / metabolism Vitronectin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council; //British Heart Foundation |
| Chemical | |
Reg. No./Substance:
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0/Fluorescent Dyes; 0/Naphthalenesulfonates; 0/Plasminogen Activator Inhibitor 1; 0/Recombinant Proteins; 0/Somatomedins; 0/Vitronectin; 36930-63-9/1,5-I-AEDANS; 63774-77-6/somatomedin B |
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