Kiewitz, Sebastian D. and Kakizawa, Taeko and Kiso, Yoshiaki and Cabrele, Chiara (2008) Switching from the unfolded to the folded state of the helix-loop-helix domain of the Id proteins based on the O-acyl isopeptide method. JOURNAL OF PEPTIDE SCIENCE, 14 (11). pp. 1209-1215. ISSN 1075-2617,
Full text not available from this repository. (Request a copy)Abstract
The inhibitors of DNA binding and cell differentiation Id 1-4 are helix-loop-helix (HLH) proteins that negatively regulate DNA transcription by forming inactive dimers with ubiquitous and tissue-specific bHLH proteins, including E47 and MyoD, respectively. Their highly conserved HLH domains are essential for heterodimerization, but can also self-associate to highly stable, alpha-helix-rich structures at low micromolar peptide concentrations. Here, we show that the introduction of an O-acyl isodipeptide unit involving the putative N-cap serine residue of the C-terminal helix completely abrogates the propensity of the Id HLH analogue for any secondary and tertiary structure, resulting in a random coil, as shown by CD measurements in nonbuffered aqueous solutions. However, the HLH fold reappears as soon as an O -> N intramolecular acyl migration, which occurs spontaneously under physiological conditions, restores the native N-cap serine residue. These results show that changes addressing the N-terminus of the C-terminal helix can dramatically influence the HLH structure, and suggest that local interactions at the junction between the loop and the C-terminal helix might be crucial during the HLH folding process. Furthermore, the present study contributes to the evaluation of the O-acyl isodipeptide unit as a powerful tool to introduce a conformational switch into peptides. Copyright (C) 2008 European Peptide Society and John Wiley & Sons, Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SEQUENCE-CONTAINING PEPTIDES; BIOLOGY-ORIENTED SYNTHESIS; ISODIPEPTIDE UNIT; DEPSIPEPTIDE TECHNIQUE; EFFICIENT SYNTHESIS; AMYLOID DEPOSITS; BETA-FIBRILLOSES; PSEUDO-PROLINES; CLICK PEPTIDE; DNA-BINDING; helix-loop-helix motif; Id proteins; O-acyl isopeptide; O -> N acyl migration; conformation switch |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Oct 2020 06:34 |
| Last Modified: | 21 Oct 2020 06:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30114 |
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