title: Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium binding protein and the nuclear p120 ribonucleoprotein.
abstract: Epstein-Barr virus/C3d receptor (CR2, CD21) interacts with three intracellular proteins: the p53 anti-oncoprotein expressed in human B lymphoma cells, the p68 calcium binding protein expressed in normal B lymphocytes and the nuclear p120 ribonucleoprotein (RNP). We previously demonstrated that p53 and p68 interacted with the intracytoplasmic carboxy-terminal domain of CR2. To analyse the amino acid sequence of CR2 binding sites for p53 and p68, we synthesized different peptides whose sequences were derived from this carboxy-terminal domain. Thus, CR2 bound to p53 and p68 through two distinct binding sites localized on the N-terminal and on the central part of its carboxy-terminal domain, characterized by the amino acid sequences of KHRERNYYTD and KEAFHLEARE, respectively. CR2 site reacting with the nuclear p120RNP was determined using either anti-CR2 mAb directed against its extracellular domain or pep34, pep14/SCR3 and pep14/SCR4, synthetic peptides whose sequences corresponded to the intracellular 34 amino acid domain or to sites of the extracellular domain of CR2, respectively. Data support that CR2 interacts with p120RNP through the DEGYRLQGPPSSRC amino acid sequence of its extracellular SCR4 domain. Furthermore, phosphorylation of CR2 inhibits its interaction with the nuclear p120RNP. Binding of CR2, through its intracellular and extracellular domains, with the p53 oncoprotein and p120RNP, respectively, and the co-localization of these three proteins on nuclear interchromatin fibrils, suggest that CR2 could act as a crosslinker between these two nuclear proteins to regulate their functions.
authors.affiliation: INSERM U.354, Centre INSERM, Hôpital Saint-Antoine, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Barel
authors.forename: M
authors.initials: M
authors.lastname: Balbo
authors.forename: A
authors.initials: A
authors.lastname: Gauffre
authors.forename: R
authors.initials: R
authors.lastname: Frade
mesh_terms: D000595:Amino Acid Sequence; D017317:Annexin A6; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D017464:Receptors, Complement 3d / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D017317:Annexin A6; D002135:Calcium-Binding Proteins; D008024:Ligands; D010455:Peptides; D017464:Receptors, Complement 3d; D011991:Receptors, Virus; D012261:Ribonucleoproteins; D016159:Tumor Suppressor Protein p53