Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks Export

@article{citeulike:410991, abstract = {Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or \^{a}€{\oe}linear motif\^{a}€� (e.g., SH3 binding to PxxP). Many domains are known, though comparatively few linear motifs have been discovered. Their short length (three to eight residues), and the fact that they often reside in disordered regions in proteins makes them difficult to detect through sequence comparison or experiment. Nevertheless, each new motif provides critical molecular details of how interaction networks are constructed, and can explain how one protein is able to bind to very different partners. Here we show that binding motifs can be detected using data from genome-scale interaction studies, and thus avoid the normally slow discovery process. Our approach based on motif over-representation in non-homologous sequences, rediscovers known motifs and predicts dozens of others. Direct binding experiments reveal that two predicted motifs are indeed protein-binding modules: a DxxDxxxD protein phosphatase 1 binding motif with a K D of 22 \^{I}¼M and a VxxxRxYS motif that binds Translin with a K D of 43 \^{I}¼M. We estimate that there are dozens or even hundreds of linear motifs yet to be discovered that will give molecular insight into protein networks and greatly illuminate cellular processes.}, address = {European Molecular Biology Laboratory, Heidelberg, Germany.}, author = {Neduva, Victor and Linding, Rune and Su-Angrand, Isabelle and Stark, Alexander and Masi, Federico and Gibson, Toby J. and Lewis, Joe and Serrano, Luis and Russell, Robert B.}, citeulike-article-id = {410991}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.0030405}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16279839}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16279839}, day = {15}, doi = {10.1371/journal.pbio.0030405}, issn = {1545-7885}, journal = {PLoS Biol}, keywords = {bioinformatic, jc\_pliage, network}, month = {November}, number = {12}, pages = {e405+}, posted-at = {2006-05-30 13:29:11}, priority = {2}, publisher = {Public Library of Science}, title = {Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks}, url = {http://dx.doi.org/10.1371/journal.pbio.0030405}, volume = {3}, year = {2005} }

TY - JOUR ID - citeulike:410991 L3 - citeulike-article-id:410991 N2 - Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or “linear motif� (e.g., SH3 binding to PxxP). Many domains are known, though comparatively few linear motifs have been discovered. Their short length (three to eight residues), and the fact that they often reside in disordered regions in proteins makes them difficult to detect through sequence comparison or experiment. Nevertheless, each new motif provides critical molecular details of how interaction networks are constructed, and can explain how one protein is able to bind to very different partners. Here we show that binding motifs can be detected using data from genome-scale interaction studies, and thus avoid the normally slow discovery process. Our approach based on motif over-representation in non-homologous sequences, rediscovers known motifs and predicts dozens of others. Direct binding experiments reveal that two predicted motifs are indeed protein-binding modules: a DxxDxxxD protein phosphatase 1 binding motif with a K D of 22 μM and a VxxxRxYS motif that binds Translin with a K D of 43 μM. We estimate that there are dozens or even hundreds of linear motifs yet to be discovered that will give molecular insight into protein networks and greatly illuminate cellular processes. IS - 12 JF - PLoS Biol SN - 1545-7885 AD - European Molecular Biology Laboratory, Heidelberg, Germany. TI - Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks PB - Public Library of Science VL - 3 SP - e405 KW - bioinformatic KW - jc_pliage KW - network AU - Neduva, Victor AU - Linding, Rune AU - Su-Angrand, Isabelle AU - Stark, Alexander AU - Masi, Federico AU - Gibson, Toby AU - Lewis, Joe AU - Serrano, Luis AU - Russell, Robert PY - 2005/11/15/ UR - http://dx.doi.org/10.1371/journal.pbio.0030405 ER -