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    The metastasis-associated extracellular matrix protein Osteopontin forms transient structure in ligand interaction sites

    Platzer, G. and Schedlbauer, A. and Chemelli, A. and Ozdowy, P. and Coudevylle, N. and Auer, R. and Kontaxis, G. and Hartl, M. and Miles, Andrew J. and Wallace, Bonnie A. and Glatter, O. and Bister, K. and Konrat, R. (2011) The metastasis-associated extracellular matrix protein Osteopontin forms transient structure in ligand interaction sites. Biochemistry 50 (27), pp. 6113-6124. ISSN 0006-2960.

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    Osteopontin (OPN) is an acidic hydrophilic glycophosphoprotein that was first identified as a major sialoprotein in bones. It functions as a cell attachment protein displaying a RGD cell adhesion sequence and as a cytokine that signals through integrin and CD44 cell adhesion molecules. OPN is also implicated in human tumor progression and cell invasion. OPN has intrinsic transforming activity, and elevated OPN levels promote metastasis. OPN gene expression is also strongly activated in avian fibroblasts simultaneously transformed by the v-myc and v-mil(raf) oncogenes. Here we have investigated the solution structure of a 220-amino acid recombinant OPN protein by an integrated structural biology approach employing bioinformatic sequence analysis, multidimensional nuclear magnetic resonance spectroscopy, synchrotron radiation circular dichroism spectroscopy, and small-angle X-ray scattering. These studies suggest that OPN is an intrinsically unstructured protein in solution. Although OPN does not fold into a single defined structure, its conformational flexibility significantly deviates from random coil-like behavior. OPN comprises distinct local secondary structure elements with reduced conformational flexibility and substantially populates a compact subspace displaying distinct tertiary contacts. These compacted regions of OPN encompass the binding sites for αVβIII integrin and heparin. The conformational flexibility combined with the modular architecture of OPN may represent an important structural prerequisite for its functional diversity.


    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 15 Aug 2011 15:45
    Last Modified: 02 Aug 2023 16:56


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