Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking. |
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Authors: | D Xu K Baburaj C B Peterson Y Xu |
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Affiliation: | Computational Biology Section, Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6480, USA. xud@ornl.gov |
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Abstract: | The structure of vitronectin, an adhesive protein that circulates in high concentrations in human plasma, was predicted through a combination of computational methods and experimental approaches. Fold recognition and sequence-structure alignment were performed using the threading program PROSPECT for each of three structural domains, i.e., the N-terminal somatomedin B domain (residues 1-53), the central region that folds into a four-bladed beta-propeller domain (residues 131-342), and the C-terminal heparin-binding domain (residues 347-459). The atomic structure of each domain was generated using MODELLER, based on the alignment obtained from threading. Docking experiments between the central and C-terminal domains were conducted using the program GRAMM, with limits on the degrees of freedom from a known inter-domain disulfide bridge. The docked structure has a large inter-domain contact surface and defines a putative heparin-binding groove at the inter-domain interface. We also docked heparin together with the combined structure of the central and C-terminal domains, using GRAMM. The predictions from the threading and docking experiments are consistent with experimental data on purified plasma vitronectin pertaining to protease sensitivity, ligand-binding sites, and buried cysteines. |
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Keywords: | 1afp [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1afp] 1gen [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1gen] 1ck7 [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1ck7] 1b4w [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1b4w] 1dmc [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1dmc] 1hpn [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1hpn] vitronectin protein structure prediction domains threading docking heparin |
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