Identification of a human estrogen receptor alpha-derived antiestrogenic peptide that adopts a polyproline II conformation

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TitleIdentification of a human estrogen receptor alpha-derived antiestrogenic peptide that adopts a polyproline II conformation
Publication TypeJournal Article
Year of Publication2009
AuthorsKapitan, J, Gallo D, Goasdoue N, Nicaise M, Desmadril M, Hecht L, Leclercq G, Barron LD, Jacquot Y
JournalJournal of Peptide Science
Volume15
Issue7
Pagination455-464
Date PublishedJul
ISBN Number1075-2617
Accession NumberISI:000267497600002
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(321)AEPPILYSEY(331)) 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-NH2) 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 alpha 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. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.

URL<Go to ISI>://000267497600002
DOI10.1002/psc.1136
Short TitleIdentification of a human estrogen receptor alpha-derived antiestrogenic peptide that adopts a polyproline II conformation
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