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Proteins. 2001 Aug 15;44(3):312-20.

Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking.

Author information

1
Computational Biology Section, Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6480, USA. xud@ornl.gov

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.

PMID:
11455604
DOI:
10.1002/prot.1096
[Indexed for MEDLINE]

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