title: Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking.
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.
authors.affiliation: Computational Biology Section, Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6480, USA. xud@ornl.gov
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: K
authors.initials: K
authors.lastname: Baburaj
authors.forename: C B
authors.initials: CB
authors.lastname: Peterson
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology; D004220:Disulfides / Q000737:chemistry; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013002:Somatomedins / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D019096:Vitronectin / Q000737:chemistry*
chemical_list: D004220:Disulfides; D013002:Somatomedins; D013438:Sulfhydryl Compounds; D019096:Vitronectin; C016756:somatomedin B; D006493:Heparin