Common molecular scaffold for two unrelated RGD molecules.
The sequence arginine-glycine-aspartic acid (RGD) is important for recognition of cell adhesion proteins by cell surface receptors (integrins). This tripeptide sequence is present in a number of proteins including fibronectin, vitronectin, von Willebrand factor and fibrinogen. Specific and selective binding of the RGD sequence by different receptors suggests that the conformational orientation of the tripeptide is critical for stereochemical recognition. The crystal structures of two proteins that contain the RGD signal were determined: (i) the cell-binding type III module of fibronectin (FNIII10) and (ii) an anti-receptor antibody fragment (OPG2) that is a functional RGD ligand mimic with an RYD recognition site in the variable (VH) domain. Both of these modules are folded into beta-barrels with two layers of antiparallel beta-sheets enclosing a hydrophobic core. Since these molecules each contain the RGD (RYD) sequence, there is a unique opportunity for direct structural comparison. The comparison has defined a common molecular scaffold in these two unrelated molecules. Within this framework, the RGD (RYD) sites are located in structurally related loops in the two modules, i.e. at one end of the scaffold in a long loop connecting the last two strands in one of the beta-sheets. This shared scaffold is used for the stereochemical presentation of the RGD site for receptor recognition.
Ely
K R
KR
Structural Biology Program, La Jolla Cancer Research Foundation, CA 92037, USA.
Kunicki
T J
TJ
Kodandapani
R
R
D000595:Amino Acid Sequence; D005353:Fibronectins / Q000737:chemistry*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D016023:Integrins / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
D005353:Fibronectins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid