title: Structural criteria of biologically active RGD-sites for analysis of protein cellular function - a bioinformatics study.
abstract: BACKGROUND
  Cell adhesion involves interactions of integrins and extracellular proteins, often facilitated by the RGD motif. Only presence of the RGD in a sequence of a protein may be not sufficient for the biological activity (binding to an integrin) and additional biochemical and/or structural studies are essential.
  
  
  METHODS
  Structural criteria that would allow identification biologically active RGD-sites on the base of a spatial structure may assist analysis of function of a protein in the cell. For the first time, computational analysis of RGD-sites in a large non-redundant set of protein structures was done.
  
  
  RESULTS
  Out of 3819 protein chains sequences of about 100 contained RGDs. Analysis of the structures of the RGD-'native' proteins has allowed establishing main determinants of the biologically active conformations of the RGD sites: surface accessibility of the whole RGD-sequence and the secondary structure. The criteria, applied to the remaining proteins of the set, identify 23 proteins ( approximately 25%) with potentially active RGD-sites. The results strongly suggest that RGD has a high propensity for being involved in protein-protein interactions and this may explain occurrence of RGDs in intracellular proteins. Results of the analysis suggest (in some cases, confirm) novel integrin-related activities for 7 membrane/extracellular proteins, as well as confirm RGD-facilitated cell attachment for 5 viral proteins.
  
  
  CONCLUSIONS
  Only presence of RGD in a sequence is not sufficient to propose biological activity of this site. The results also suggest that the method can be used on large scale: for example, for identifying potential integrin-interacting proteins in an animal genome.
authors.affiliation: Laboratory of Kinetics and CLaboratory Of Chemical Kinetics And Catalysis, Chair Of Physical Chemistry, Department of Chemistry, Moscow State University, Moscow, Russia. biotiy@suez.cs.gsu.edu
authors.forename: Ivan Y
authors.initials: IY
authors.lastname: Torshin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D019483:Disintegrins / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry
chemical_list: D019483:Disintegrins; D016023:Integrins; D009842:Oligopeptides; D011506:Proteins; D011971:Receptors, Immunologic; C047981:arginyl-glycyl-aspartic acid