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• W2104730963 abstract "The activator protein-1 (AP-1) complex plays a crucial role in numerous pathways, and its ability to induce tumorigenesis is well documented. Thus, AP-1 represents an interesting therapeutic target. We selected peptides from phage display and compared their ability to disrupt the cFos/cJun interaction to a previously described in vivo protein-fragment complementation assay (PCA). A cJun-based library was screened to enrich for peptides that disrupt the AP-1 complex by binding to the cFos coiled-coil domain. Interestingly, phage display identified one helix, JunW(Ph1) [phage-selected winning peptide (clone 1) targeting cFos], which differs in only 2 out of 10 randomized positions to JunW (PCA-selected winning peptide targeting cFos). Phage-selected peptides revealed higher affinity to cFos than wild-type cJun, harboring a T(m) of 53 degrees C compared to 16 degrees C for cFos/cJun or 44 degrees C for cFos/JunW. In PCA growth assays in the presence of cJun as competitor, phage-selected JunW(Ph1) conferred shorter generation times than JunW. Bacterial growth was barely detectable, using JunW(Ph1) as a competitor for the wild-type cJun/cFos interaction, indicating efficient cFos removal from the dimeric wild-type complex. Importantly, all inhibitory peptides were able to interfere with DNA binding as demonstrated in gel shift assays. The selected sequences have consequently improved our 'bZIP coiled-coil interaction prediction algorithm' in distinguishing interacting from noninteracting coiled-coil sequences. Predicting and manipulating protein interaction will accelerate the systems biology field, and generated peptides will be valuable tools for analytical and biomedical applications." @default.
• W2104730963 created "2016-06-24" @default.
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• W2104730963 date "2008-08-01" @default.
• W2104730963 modified "2023-09-23" @default.
• W2104730963 title "Selectional and Mutational Scope of Peptides Sequestering the Jun–Fos Coiled-Coil Domain" @default.
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• W2104730963 doi "https://doi.org/10.1016/j.jmb.2008.04.030" @default.
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