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Towards a proteome-scale map of the human protein-protein interaction network
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One of the first publications of genome-scale yeast two-hybrid studies involving human proteins. This study identified some 2800 interactions involving 1549 proteins. The data reveals more than 300 new connections to over 100 disease-associated proteins.
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Rual J.F., Venkatesan K., Hao T., Hirozane-Kishikawa T., Dricot A., Li N., Berriz G.F., Gibbons F.D., Dreze M., Ayivi-Guedehoussou N., et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 437 (2005) 1173-1178. One of the first publications of genome-scale yeast two-hybrid studies involving human proteins. This study identified some 2800 interactions involving 1549 proteins. The data reveals more than 300 new connections to over 100 disease-associated proteins.
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One of the first publications on genome-scale yeast two-hybrid studies involving human proteins. This study identified some 3186 interactions involving 1705 proteins. The interaction map links 195 disease-related proteins to previously unidentified partners, allows the description of 342 uncharacterized human proteins via their interactions, and suggests new roles for hundreds of known proteins.
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Stelzl U., Worm U., Lalowski M., Haenig C., Brembeck F.H., Goehler H., Stroedicke M., Zenkner M., Schoenherr A., Koeppen S., et al. A human protein-protein interaction network: a resource for annotating the proteome. Cell 122 (2005) 957-968. One of the first publications on genome-scale yeast two-hybrid studies involving human proteins. This study identified some 3186 interactions involving 1705 proteins. The interaction map links 195 disease-related proteins to previously unidentified partners, allows the description of 342 uncharacterized human proteins via their interactions, and suggests new roles for hundreds of known proteins.
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A rare example of a small-molecule capable of disrupting a large interaction surface, specifically those interactions involved in the formation of the tumor necrosis factor (TNF) trimer. The compound causes trimer dissociation and thus inhibition of the TNFα pathway.
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Describes how protein arrays can be used to map peptide-mediated interactions of a particular class (phosphorylated tyrosines). A protein array of all human phosphotyrosine-binding modules was probed with 61 peptides representing physiological tyrosine phosphorylation sites on the four ErbB receptors, leading to a comprehensive view of potential phosphotyrosine-mediated interactions for this protein family. At higher concentrations the oncogenic ErbB1 and ErbB2 become more promiscuous than ErbB3, possibly explaining part of their role in pathogenesis.
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The first systematic attempt to uncover new interactions mediated by linear motifs. The authors looked for over-represented sequence patterns within all sets of proteins sharing an interaction partner from genome-scale interaction data from yeast, fly, nematode and human. They re-discovered many known motifs (SH3/PxxP etc.) and predicted many others that were completely new. For two new motifs they demonstrated that peptides containing the motif bound directly to the predicted partner.
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This paper introduces DILIMOT: a method for finding potential linear motifs mediating an interaction or some other common function, such as cellular location, shared by a set of sequences.
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Neduva V., and Russell R.B. DILIMOT: Discovery of linear motifs in proteins. Nucleic Acids Res 34 Web Server issue (2006) W350-W355. This paper introduces DILIMOT: a method for finding potential linear motifs mediating an interaction or some other common function, such as cellular location, shared by a set of sequences.
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Among the first examples of a synthetic small-molecule inhibitor disrupting a peptide- (and in this case a linear motif) mediated interaction: the interaction between MDM2 and p53. The study demonstrates the possibility of using traditional drug discovery techniques (i.e. chemical library screens, competitions assays, etc.) to develop compounds that act on medically important protein interactions directly.
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An intriguing example of subtle functional regulation through selective disruption of different peptide-mediated interactions, specifically between G-protein βγ subunits and various binding partners. Small-molecules could be found that selectively disrupt protein interactions with the canonical G-protein βγ subunit partners and differentially modulate functions downstream of G-protein-coupled receptors.
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A structural explanation of the synergistic effect resulting from the simultaneous binding of a small-molecule toxin and a linear motif containing peptide. The structure of a plant 14-3-3 protein bound to both a toxin and one of its natural ligands showed that they occupied adjacent parts of the same pocket, explaining how the interaction was made 90-fold stronger in the presence of the toxin.
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