Integrin sequences, cell surface

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

Probably the smallest sequence known to be responsible for receptor recognition is the RGD-tripeptide, initially discovered in fibronectin [143]. However, the specificity of the interaction with different integrins, the counter receptors of RGD sequences on the cell surface, is established by the flanking sequences of the RGD motif and the conformation of the tripeptide. In other words, the presentation of the RGD sequence is important for specific recognition by individual integrins. 

The domain structure in fibronectins is made up of a few types of peptide module that are repeated numerous times. Each of the more than 50 modules is coded for by one exon in the fibronectin gene. Alternative splicing (see p. 246) of the hnRNA transcript of the fibronectin gene leads to fibronectins with different compositions. The module that causes adhesion to cells contains the characteristic amino acid sequence -Arg-Gly-Asp-Ser-. It is these residues that enable fibronectin to bind to cell-surface receptors, known as integrins. 

Recently, TTR1 fibrils have been decorated with the classic RGD tripeptide motif isolated from fibronectin, which encourages cell adhesion via integrin cell surface receptors (Gras et al., 2008). This bioactive tag was added to the TTR1 sequence which drives fibril assembly and the tag shown to be exposed on the fibril surface and accessible to cells following assembly. The RGD-modified fibrils were bioactive in a cell dissociation assay which measures the ability of fibrils to competitively bind to cells and induce cell detachment from a surface, as illustrated in Figure 19. In... 

The extracellular domains of integrins interact with a variety of profeins of the extracellular matrix. These include fibronectin, fibrinogen, vifronecfin, collagen, and entacfin. Other large cell surface adhesins include laminin and osteopontin (Chapfer 8), thrombospondin, von Willebrand factor, and related proteins. These adhesins appear to depend upon the sequence Arg-Gly-Asp (RGD), which binds nonco-valently to integrins, which act as cell-surface receptors. See also Chapter 12, Section C,9. 

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