Fibronectin module

Potts, J.R. and Campbell, I.D. (1996) Structure and function of fibronectin modules. Matrix Biology 15,... 

Spiegelman BM, Ginty CA (1983) Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes. Cell 35(3 Pt 2) 657-666... 

Following the tandem repeat sequences, four unc structural motifs are present in all three smooth muscle MLCKs but not in the skeletal muscle enzymes. The unc motifs are repeat structures of approximately 100 amino acids found in twitchin, the Cae-norhabditis elegans unc-22 gene product. Motif 1 is related to the type 111 module of fibronectin (Campbell and Spitzfaden, 1994) and is N-terminal of the catalytic core (Fig. 3). The general topology of this fibronectin module contains seven antiparallel p-strands ar-... 

Figure 3. The most Stable initial adsorption geometry of the albumin A subdomain at left showing large rearrangements of the most hydrophobic a-helix in contact with the surface, while minor changes are observed for the fibronectin module at right.

Figure Interaction energy Emt (left) and stretin energy E,train (right) plotted as a function of tisoa. The results obtained for the two albumin subdomains in dififerent orientations are stained for the two albumin subdomains in different orientations are shown with empty symbol, and for the fibronectin module with full symbols. The solid lines are the best-fit lines through the origin given by eqs. (1) and (2).

Figure 5. Side and top view of two best adsorption geometry after the MD runs and subsequent energy minimizations. At left we show the albumin A subdomain, and at right the fibronectin module. Note the lack of any secondary structure in both...

Both albumin subdomains show an extensive denaturation with the formation of a monolayer of amino acids. Such a large molecular spreading on the surface is consistent with experimental data obtained for the whole protein on a hydrophobic surface [15]. On the other hand, for the fibronectin module it is more difficult to form a monolayer on the graphite surface because it contains four disulfide bridges acting as intramolecular crosslinks. We studied how such crosslinks affect or even hinder the conformational changes during the MD runs by per-... 

In the most stable state, found after optimization of many selected snapshots, the fibronectin module and the albumin subdomains optimize the surface interaction by spreading as much as possible, thus maximiz-... 

Figure 8. Radius of gyration ind its squared components calculated during the MD runs of the fibronectin module already shown in Figure 6.

Figure 9. Pair distribution function (PDF) of the oxygen atoms of the water molecules around the backbone of the two albumin subdomains in the initial and final adsorption state (left), and around the backbone of the fibronectin module as an isolated molecule and in the final adsorption state (right).

In the present paper we review our recent work on the adsorption of two albumin subdomains and a fibronectin module on a graphite surface by atomistic simulations through energy minimizations and molecular dynamics runs. We adopted a simulation strategy in two-steps to study the initial and the final adsorption state on a bare surface in a dielectric medium and in the explicit presence of the solvent. 

Kao, W.J. et al, Fibronectin modulates macrophage adhesion and FBGC formation the role of RGD, PHSRN, and PRRARV domains, /. Biomed. Mater. Res., 55,79,2001. 

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