RGD receptor

Alon, R, Bayer, E A, and Wilcheck, M (1990) Streptavidin contains an Ryd sequence which mimics the RGD receptor domain of fibronectin Biochem Biophys Res. Commun 170, 1236—1241... 

FMDV is the outlier of picornavirus structures (Fry et al, 1990), with capsid proteins that are 20% shorter than in the other viruses. The VPl loops near the 5-fold axis are sheared off, so that there is not the pronounced 5-fold protrusion and canyon of rhinoviruses and polioviruses (Acharya et al, 1989). This leaves a longer VPl GH loop as the prominent surface feature, which is highly antigenic, the site of the RGD receptor attachment sequence, but disordered in structure unless a disulfide is reduced (Acharya et al, 1989 Fox et al, 1989 Lea et al, 1994 Rowlands et al, 1994). FMDV VP2 is more similar to its homologs, except that the GH loop puff is 50 residues shorter than in poliovirus, and its space is occupied pardy by the longer VPl GH loop. 

The hydantoin moiety has been utilized as a biostere for the peptide linkage, transforming a peptide lead into an orally available drug candidate. Therefore, an Arg-Gly-Asp-Ser tetrapeptide (18) lead structure was modified to a non-peptide RGD mimetic as an orally active fibrinogen receptor antagonist 19. ° ... 

Horton MA, Taylor ML, Arnett TR et al (1991) Arg-Gly-Asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp Cell Res 195 368-375... 

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.

Other adhesion receptors that are structurally and functionally related include the receptors for fibronectin, vitronectin, platelet glycoproteins 13b and Ilia and the VLA (very-late antigen) series. All molecules involved in adhesion recognise the RGD motif and require the divalent cations Ca2+ and Mg2+ for binding. All are dimers of glycosylated proteins with relative molecular masses 95-190 kDa. There is also some sequence homology between the /J-chain (CD18) and one chain of the fibronectin receptor. 

Integrin receptor-binding peptides have been used to enhance liposome binding, uptake, and expression (25,47 9). The inclusion of an 0(5pi integrin-targeted peptide into a liposomal complex enhanced transfection efficiency four- to five-fold in Jurkat cells and 10- to 13-fold in TF-1 cells (48). Confocal and electron microscopy revealed that the mechanism of cell entry conferred by RGD peptides on liposomes is predominantly by clathrin-coated endocytosis rather than by phagocytosis (50). 

The possibility of binding RGD to different receptors is probably caused by a different spatial conformation of RGD due to the vicinity of different amino acids or existence of different synergistic sequences on various extracellular matrix (ECM) molecules. At the same time, one type of integrin can bind more ligands [38-40]. 

Although the single amino acids cannot bind the adhesion receptors on cells, they provide other ehemieal functional groups which may improve the adsorption of eell adhesion-mediating molecules on the material surface. Similar efifeet was observed on ion-implanted polyethylene grafted with the Arg-Gly-Asp (RGD)... 

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. 

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