2015
DOI: 10.1021/acs.jpcb.5b09824
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Conformational Diversity of the Helix 12 of the Ligand Binding Domain of PPARγ and Functional Implications

Abstract: Nuclear hormone receptors (NR) are transcription factors that activate gene expression in response to ligands. Structural and functional studies of the ligand binding domains (LBD) of NRs revealed that the dynamics of their C-terminal helix (H12) is fundamental for NR activity. H12 is rigid and facilitates binding of coactivator proteins in the agonist-bound LBD. In the absence of ligand, H12 exhibits increased flexibility. To provide a comprehensive picture of the H12 conformational equilibrium, extensive mol… Show more

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Cited by 14 publications
(17 citation statements)
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“…In contrast, H12 was positioned closer to the empty binding cavity from our atomistic and CG MD simulations, compared to the initial structure. Furthermore, this observation is in agreement with a previous study on H12 of PPARγ which showed H12 is limited to local movements at ordinary temperatures39.…”
Section: Discussionsupporting
confidence: 93%
“…In contrast, H12 was positioned closer to the empty binding cavity from our atomistic and CG MD simulations, compared to the initial structure. Furthermore, this observation is in agreement with a previous study on H12 of PPARγ which showed H12 is limited to local movements at ordinary temperatures39.…”
Section: Discussionsupporting
confidence: 93%
“…Both the larger conformational freedom of helix 12 in apo‐PPARγ, as well as helix 12 conformations similar to those observed by X‐ray crystallography in the type A and type B chains [Fig. (C,D)] have recently been reproduced in MD simulations …”
Section: Resultssupporting
confidence: 52%
“…Interestingly, in these structures, helix 12 of the type B chains is positioned roughly in the coactivator groove of the type A chains. Recently, a role for conformations similar to the type B chains in the binding of transcriptional corepressors has been suggested by MD simulations of PPARα . In summary, a more complete understanding of the role of PPARγ conformers similar to the type B chains requires further study.…”
Section: Resultsmentioning
confidence: 99%
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“…Part of this peptide corresponds to the region that changes more its position between the studied ERβ LBD conformations. The use of reaction coordinates based on the RMSD of the region of the protein known to be important for the conformational change provides a more accurate description of the process pathways 11, 62 . Each RMSD coordinate covered a range of 1 to 10 Å.…”
Section: Methodsmentioning
confidence: 99%