PMID- 17258904 OWN - NLM STAT- MEDLINE DCOM- 20070510 LR - 20070319 IS - 0960-0760 (Print) IS - 0960-0760 (Linking) VI - 104 IP - 1-2 DP - 2007 Apr TI - Estrogen receptor alpha--identification by a modeling approach of a potential polyproline II recognizing domain within the AF-2 region of the receptor that would play a role of prime importance in its mechanism of action. PG - 1-10 AB - Estrogen receptors (ERs) behave not only as ligand-dependent transcriptional factors; they can also trigger non-genomic responses involving mitogen activated protein kinases (MAPKs), reported to be crucial in transduction cascades. MAPKs are partially activated by proteins with domains able to interact with polyproline II (PPII) regions. Recent studies have brought up the direct interaction of PPII-containing proteins with the alpha subtype human ER (ERalpha). Such observations suggest that ERalpha may contain a "PPII recognizing domain" (PRD). By sequence alignment, we identified such a potential PRD within the AF-2 region of ERalpha (residues 351-414). According to our modeling studies based on X-ray structural data, this PRD appears to be divided in two sub-regions known to interact with alpha-helix containing coactivators. Our data also reveal the potential existence of intramolecular interactions of this domain with a large PPII-rich region of the receptor (residues 301-330). Implication of these regulatory structural elements in both genomic and non-genomic responses seems likely. FAU - Jacquot, Yves AU - Jacquot Y AD - Universite Pierre et Marie Curie-Paris 6, CNRS, UMR 7613, Synthese, Structure et Fonction de Molecules Bioactives, FR 2769, Case courrier 45, 4, place Jussieu, 75005 Paris, France. jacquot@ccr.jussieu.fr FAU - Gallo, Dominique AU - Gallo D FAU - Leclercq, Guy AU - Leclercq G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070129 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Estrogen Receptor alpha) RN - 0 (Ligands) RN - 0 (Peptides) RN - 25191-13-3 (polyproline) SB - IM MH - Amino Acid Sequence MH - Crystallography, X-Ray MH - Estrogen Receptor alpha/*chemistry MH - Humans MH - Ligands MH - *Models, Biological MH - Molecular Sequence Data MH - Peptides/*chemistry/metabolism MH - Protein Conformation MH - Sequence Homology, Amino Acid MH - src Homology Domains EDAT- 2007/01/30 09:00 MHDA- 2007/05/11 09:00 CRDT- 2007/01/30 09:00 PHST- 2006/06/22 00:00 [received] PHST- 2006/10/02 00:00 [accepted] PHST- 2007/01/30 09:00 [pubmed] PHST- 2007/05/11 09:00 [medline] PHST- 2007/01/30 09:00 [entrez] AID - S0960-0760(06)00349-9 [pii] AID - 10.1016/j.jsbmb.2006.10.008 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2007 Apr;104(1-2):1-10. doi: 10.1016/j.jsbmb.2006.10.008. Epub 2007 Jan 29.