Solution structure of a type 2 module from fibronectin: implications for the structure and function of the gelatin-binding domain

Andrew R Pickford, Jennifer R Potts, Jeremy R Bright, Isabelle Phan, Iain D Campbell
1997 Structure  
Fibronectin is an extracellular matrix glycoprotein involved in cell adhesion and migration events in a range of important physiological processes. Aberrant adhesion of cells to the matrix may contribute to the breakdown of normal tissue function associated with various diseases. The adhesive properties of fibronectin may be mediated by its interaction with collagen, the most abundant extracellular matrix protein. The collagen-binding activity of fibronectin has been localized to a 42 kDa
more » ... lytic fragment on the basis of this fragment's affinity for denatured collagen (gelatin). This gelatin-binding domain contains the only type 2 (F2) modules found in the protein. The F2 modules of the matrix metalloproteinases MMP2 and MMP9 are responsible for the affinity of these proteins for gelatin. Knowledge of the structure of fibronectin will provide insights into its interactions with other proteins, and will contribute to our understanding of the structure and function of the extracellular matrix, in both normal and disease-altered tissues. Results: We have determined the solution structure of the first F2 ( 1 F2) module from human fibronectin by two-dimensional NMR spectroscopy. The tertiary structure of the 1 F2 module is similar to that of a shorter F2 module, PDC-109b, from the bovine seminal plasma protein PDC-109. The 1 F2 module has two double-stranded antiparallel ␤ sheets oriented approximately perpendicular to each other, and enclosing a cluster of highly conserved aromatic residues, five of which form a solvent-exposed hydrophobic surface. The N-terminal extension in 1 F2 brings the N and C termini of the module into close proximity. Conclusions: The close proximity of the N and C termini in 1 F2 allows for interactions between non-contiguous modules in the gelatin-binding domain. Thus, instead of forming an extended, linear chain of modules, the domain may have a more compact, globular structure. A pocket in the module's solventexposed hydrophobic surface may bind nonpolar residues in the putative fibronectin-binding site of the extracellular matrix component type I collagen. Research Article 359 *Proton chemical shifts were measured relative to dioxane at 3.75 ppm; (-) indicates an unassigned or unobserved resonance. † Protons with degenerate chemical shifts.
doi:10.1016/s0969-2126(97)00193-7 pmid:9083105 fatcat:cyajmgoxljfdfivstrpclrrr5q