title: Recognition sequences for the GYF domain reveal a possible spliceosomal function of CD2BP2.
abstract: Protein-protein interactions are often mediated by small domains that recognize solvent-exposed peptide sequences. Deciphering the recognition code for these adapter domains is an important step in the understanding of multi-protein assemblies. Here, we investigate the sequence requirements for the CD2BP2-GYF domain, a proline-rich sequence binding module previously shown to be involved in T cell signaling. We show that the signature (R/K/G)XXPPGX(R/K) defines a preferred peptide-binding motif that is present in several proteins of the splicing machinery. Specifically, the core small nuclear ribonucleoprotein, SmB/B', contains several PPP-PGMR motifs that interact with the CD2BP2-GYF domain in vitro and in vivo. The colocalization of CD2BP2 and SmB proteins in the nucleus of Jurkat T cells and HeLa cells suggests a function of the GYF domain of CD2BP2 in mediating protein-protein interactions within the spliceosome.
authors.affiliation: Protein Engineering Group, Forschungsinstitut für Molekulare Pharmakologie und Freie Universität Berlin, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kofler
authors.forename: Katja
authors.initials: K
authors.lastname: Heuer
authors.forename: Tobias
authors.initials: T
authors.lastname: Zech
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019992:Databases as Topic; D005982:Glutathione Transferase / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D012984:Software; D017381:Spliceosomes / Q000378:metabolism*; D014162:Transfection; D055517:snRNP Core Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; C120378:CD2BP2 protein, human; D002352:Carrier Proteins; D008024:Ligands; D008164:Luminescent Proteins; D010455:Peptides; D017411:Ribonucleoproteins, Small Nuclear; C526407:SNRPB protein, human; D055517:snRNP Core Proteins; D049452:Green Fluorescent Proteins; D011392:Proline; D005982:Glutathione Transferase; D005998:Glycine