Selectional and Mutational Scope of Peptides Sequestering the Jun–Fos Coiled-Coil Domain

iPEP: peptides designed and selected for interfering with protein interaction and function

“…Our algorithm, unlike others to date, considers helix propensity, which is found to be integral in coiled-coil stability, in addition to electrostatic e-g and core a-a and d-d residue interactions [20,21]. Indeed, in applying the algorithm to all 59 2 bZIP interactions, we were able to correctly identify 97 % of all strong interactions and 95 % of all non-interacting pairs [17,22] (http://www.molbiotech.uni-freiburg.de/bCIPA/).…”

“…Peptides were selected from the same parent library as the PCA-selected JunW peptide using the phage-display technique to permit a direct comparison of selected sequences and the ability of these sequences to disrupt the c-Fos-c-Jun interaction [22]. Explicitly, a c-Jun-based library was screened to enrich for peptides that disrupt the AP-1 complex by binding to the c-Fos coiled-coil domain.…”

“…Importantly, all inhibitory peptides were able to interfere successfully with DNA binding as demonstrated in gel-shift assays (Figure 3). These selected sequences were used to further refine 'bCIPA' in distinguishing interacting from non-interacting coiled-coil sequences [22].…”

Photocontrol of Coiled‐Coil Proteins in Living Cells

“…[2,4,8,9] By using micro- Figure 1. Irradiation at 365 nm of an azobenzene-cross-linked AP-1 dominant negative peptide, XAFosW, causes trans-to-cis isomerization, which enhances helicity, favors a coiled-coil formation, and thereby leads to the inhibition of DNA binding.…”

“…[3,4,9,10] Indeed, coiled coils are found in a diverse range of proteins, in which they are involved not only in transcriptional control but also in muscle contraction, viral infection, cell signaling, mitochondrial import, and fertilization. Dominant negative peptide sequences are generally short enough to permit straightforward chemical synthesis by solid-phase methods; they can be unfolded and refolded easily, and the introduction of the photoswitch through reaction with Cys residues at f positions in the coiled-coil heptad repeat is a robust and quantitative reaction.…”