(a) Modular structure of the
fibronectin family. Fibronectin consists of two monomeric strands
linked by two disulfide bridges (S—S). Each monomer contains three
types of modules, types I, II, and III, and/or variable modules V.
Modules that are either inserted or missing in various spliced forms of
fibronectin are shown as filled circles. The cell adhesion site and
other recognition sites are indicated.
(b–e) Forced unfolding sequence of
FnIII10 for various extensions of the module. A different
gray scale is used to highlight the RGD motif and strand G. Hydrogen
bond pairs that are broken in clusters during the unfolding burst of
the module are displayed by dotted (AB bond pairs) and dashed (FG bond
pairs) lines. The ball-and-stick representation indicates the position
of the RGD cell binding region along the FG loop of
FnIII10. Water molecules that were included in the SMD
simulation are omitted for clarity. The equilibrated structure of
FnIII10 is shown in b with its fixed
terminal end (×) and the applied external pulling force (gray arrow).
Partial distortion of the module is evident in c with
the hydrogen bonds between strand F and G being stretched. Finally, in
d, strand G clearly is separated from β-sheet FCD with
the hydrogen bonds between F and G broken apart. Only strands C, D, and
E remain in e to form a structural unit whereas the
other strands form a line along the pulling direction. Further pulling
on the module leads to total disintegration of the module with all
strands aligned. This figure was created with molscript
(37).