Kapitan, J., Gallo, D., Goasdoue, N., Nicaise, M., Desmadril, M., Hecht, L., Leclercq, G., Barron, L.D. and Jacquot, Y. (2009) Identification of a human estrogen receptor α-derived antiestrogenic peptide that adopts a polyproline II conformation. Journal of Peptide Science, 15(7), pp. 455-464. (doi: 10.1002/psc.1136)
Full text not currently available from Enlighten.
Abstract
Polyproline II (PPII) helix is an extended secondary structure present in a number of proteins. PPII-containing sequences mediate specific protein-protein interactions with partners containing appropriate cognate domains called PPII-recognizing domains (PRDs) and are involved in the activation of intracellular signaling pathways. Thus, the identification of PPII structures in proteins is of great interest, not only to explore molecular and physiological mechanisms, but also to elaborate new potential drugs. By revisiting X-ray crystal structures of liganded alpha-type human estrogen receptor (ER alpha), we have identified an 11-residue PPII-helical sequence (D<sup>321</sup>)AEPPILYSEY<sup>331</sup>) in the ligand-binding domain of the receptor. The data recorded by far-ultraviolet circular dichroism (far-UV CD), vibrational Raman optical activity (ROA) and differential scanning calorimetry (DSC) show that the corresponding peptide (Ac-DAEPPILYSEY-NH<sub>2</sub>) is particularly well structured in PPII, with the same proportion of PPII as observed from X-ray structures (similar to 85%). In addition, studies carried out on ER alpha-negative Evsa-T breast cancer cells transiently co-transfected with a pcDNA3-ER α plasmid and a Vit-tk-Luc reporter gene revealed that the peptide antagonizes the estradiol-induced transcription providing perspectives for researching new molecules with antagonistic properties.
| Item Type: | Articles |
|---|---|
| Keywords: | ACTIVATION antiestrogenic activity BINDING-PROTEINS BREAST-CANCER CELLS CD spectroscopy CELL CIRCULAR-DICHROISM CONFORMATION CRYSTAL Crystal structure Crystal structures CRYSTAL-STRUCTURE CRYSTAL-STRUCTURES DICHROISM DOMAIN estrogen receptor IDENTIFICATION LIGAND-BINDING MECHANISM MOLECULE MOLECULES OPTICAL-ACTIVITY PATHWAY peptide POLY-L-PROLINE polyproline II PROLINE-RICH PEPTIDE PROTEIN PROTEINS Raman optical activity RAMAN OPTICAL-ACTIVITY ROA spectroscopy SECONDARY STRUCTURE SEQUENCE SEQUENCES SH3 DOMAINS SH3-BINDING MOTIF Structure UNFOLDED PROTEINS WW DOMAIN X-RAY X-RAY-STRUCTURE |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kapitan, Dr Josef and Hecht, Dr Lutz and Barron, Professor Laurence |
| Authors: | Kapitan, J., Gallo, D., Goasdoue, N., Nicaise, M., Desmadril, M., Hecht, L., Leclercq, G., Barron, L.D., and Jacquot, Y. |
| Subjects: | Q Science > Q Science (General) |
| College/School: | College of Science and Engineering > School of Chemistry |
| Journal Name: | Journal of Peptide Science |
| Publisher: | John Wiley & Sons Ltd. |
| ISSN: | 1075-2617 |
| ISSN (Online): | 1099-1387 |
| Published Online: | 07 May 2009 |
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric