1xb7

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{{STRUCTURE_1xb7| PDB=1xb7 | SCENE= }}
{{STRUCTURE_1xb7| PDB=1xb7 | SCENE= }}
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'''X-ray structure of ERRalpha LBD in complex with a PGC-1alpha peptide at 2.5A resolution'''
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===X-ray structure of ERRalpha LBD in complex with a PGC-1alpha peptide at 2.5A resolution===
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==Overview==
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The crystal structure of the ligand binding domain (LBD) of the estrogen-related receptor alpha (ERRalpha, NR3B1) complexed with a coactivator peptide from peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) reveals a transcriptionally active conformation in the absence of a ligand. This is the first x-ray structure of ERRalpha LBD, solved to a resolution of 2.5 A, and the first structure of a PGC-1alpha complex. The putative ligand binding pocket (LBP) of ERRalpha is almost completely occupied by side chains, in particular with the bulky side chain of Phe328 (corresponding to Ala272 in ERRgamma and Ala350 in estrogen receptor alpha). Therefore, a ligand of a size equivalent to more than approximately 4 carbon atoms could only bind in the LBP, if ERRalpha would undergo a major conformational change (in particular the ligand would displace H12 from its agonist position). The x-ray structure thus provides strong evidence for ligand-independent transcriptional activation by ERRalpha. The interactions of PGC-1alpha with ERRalpha also reveal for the first time the atomic details of how a coactivator peptide containing an inverted LXXLL motif (namely a LLXYL motif) binds to a LBD. In addition, we show that a PGC-1alpha peptide containing this nuclear box motif from the L3 site binds ERRalpha LBD with a higher affinity than a peptide containing a steroid receptor coactivator-1 motif and that the affinity is further enhanced when all three leucine-rich regions of PGC-1alpha are present.
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(as it appears on PubMed at http://www.pubmed.gov), where 15337744 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15337744}}
==About this Structure==
==About this Structure==
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[[Category: Nuclear hormone receptor]]
[[Category: Nuclear hormone receptor]]
[[Category: Three-layered alpha-helical sandwich]]
[[Category: Three-layered alpha-helical sandwich]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:44:55 2008''

Revision as of 17:44, 27 July 2008

Image:1xb7.png

Template:STRUCTURE 1xb7

X-ray structure of ERRalpha LBD in complex with a PGC-1alpha peptide at 2.5A resolution

Template:ABSTRACT PUBMED 15337744

About this Structure

1XB7 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha., Kallen J, Schlaeppi JM, Bitsch F, Filipuzzi I, Schilb A, Riou V, Graham A, Strauss A, Geiser M, Fournier B, J Biol Chem. 2004 Nov 19;279(47):49330-7. Epub 2004 Aug 26. PMID:15337744

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