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

Proteins. 2001 Aug 15;44(3):312-20. doi: 10.1002/prot.1096.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Computational Biology
  • Disulfides / chemistry
  • Heparin / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Folding*
  • Protein Structure, Tertiary
  • Somatomedins / chemistry
  • Sulfhydryl Compounds / chemistry
  • Vitronectin / chemistry*

Substances

  • Disulfides
  • Somatomedins
  • Sulfhydryl Compounds
  • Vitronectin
  • somatomedin B
  • Heparin