Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structural properties of the basic subdomain of the basic zipper (bZIP) protein c-Jun were examined by joint means of 1H-NMR, CD and Fourier-transform infrared (FTIR) spectroscopies. The basic subdomain (residues 252-281 in c-Jun) is responsible for sequence-specific recognition of DNA. A modified basic subdomain bSD (residues 1-35) and its N-terminal part and C-terminal part fragments (NP, residues 1-19; and, CP, residues 16-35) were prepared by solid-phase synthesis and purified by HPLC. In aqueous solution, in the absence of DNA, bSD behaved mostly as an unstructured peptide characterized by only 5% alpha helix. However, upon mixing bSD and a specific DNA fragment, i.e. a CRE(cAMP-responsive element)-containing hexadecanucleotide, the alpha helix was stabilized to an extent of 20% at 20 degrees C or 35% at 2 degrees C. At the same time, no significant change could be detected in the DNA spectra. Addition of trifluoroethanol to an aqueous bSD sample resulted in an increase of the alpha-helix content so that about 60% of alpha helix was found at a ratio of 75% trifluoroethanol (20 degrees C). These effects were reflected in both CD and FTIR measurements. Changes shown by the CD spectra during the process suggested a mechanism dominated by a two-state helix/unordered transition. NMR data, namely alpha H chemical shifts, NOE cross-peaks and NH temperature coefficients provided indications for extended or nascent helix structures within four short stretches dispersed along the sequence for c-Jun bSD, contrasting with the unique and continuous stretch reported for Gcn4 (yeast general control protein 4) bSD in aqueous solution. Trifluoroethanol stabilized the alpha-helix structure mainly at these four sites. The malleability of the basic subdomain of c-Jun was emphasized in relation to its ability to fit the DNA helix in adopting an alpha-helix structure. The complex formation apparently requires substantial conformational change from the peptide and only little from the oligonucleotide.
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PMID:The basic subdomain of the c-Jun oncoprotein. A joint CD, Fourier-transform infrared and NMR study. 763 48

In a previous paper, we reported on the structural properties of a 35-residue peptide corresponding to a modified basic subdomain (bSD) of the basic zipper protein c-Jun (residues 252-281) as determined by combined use of 1H-NMR, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopies [Krebs, D., Dahmani, B., El Antri, S., Monnot, M., Convert, O,. Mauffret, O., Troalen, F. & Fermandjian, S. (1995) Eur. J. Biochem. 231, 370-380]. The fragments NP and CP (the N-terminal residues 1-19 and C-terminal residues 16-35 of bSD, respectively) proved to be particularly useful for the assignment of the 1H-NMR spectra of the full-length bSD, which has been achieved completely in aqueous solution and partially in trifluoroethanol. Here, we report on the structural properties of NP and CP in aqueous solution and under varying H2O/trifluoroethanol conditions, again using 1H-NMR, CD and FT-IR experiments. Both CD and FT-IR results established that the fragments are weakly structured in aqueous solution. Addition of trifluoroethanol to aqueous solutions of the peptides produced their stabilization into helix, following a profile sigmoidal for NP and nearly linear for CP. Quantitative NOEs, secondary Halpha chemical shifts, NH temperature coefficients and 3JalphaN coupling constants for the peptides in aqueous solutions provided indications for weak helix features (nascent helices) manifested within two sites (continuous dNN NOEs) in both NP and CP. For each peptide, an excellent agreement was observed between experiments and predictions with the AGADIR program for the location of these nascent helices in the sequences. Trifluoroethanol provoked both the alpha-helix stabilization within these sites and the alpha-helix propagation to adjacent amino acid residues. Finally, our results reflected the high flexibility and helix potential of the NP and CP fragments, these two properties seeming crucial for the accommodation of c-Jun to its specific DNA targets. The results demonstrated also the fragmentation's benefits in dissecting a protein or a complex peptide into smaller fragments and analyzing their structure individually.
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PMID:Dissection of the basic subdomain of the c-Jun oncoprotein: a structural analysis of two peptide fragments by CD, Fourier-transform infrared and NMR. 865 20