Conserved Positions of the Ligand Pocket Residues in NRs

<p>Structure-based sequence alignment of various NR LBDs shows that ligand pocket residues (boxed by black squares) are conserved in their relative positions within the context of their secondary structural elements (labeled underneath) of NRs. All sequences are from human proteins except Seven-up, a COUP-TF-like orphan receptor from D. melanogaster. The Protein Databank (PDB; <a href="http://www.rcsb.org/pdb/home/home.do" target="_blank">http://www.rcsb.org/pdb/home/home.do</a>) codes for the ligand/receptor complexes is: 1fmr for 9cRA-bound RXRα [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b028" target="_blank">28</a>], 1lv4 for HNF4γ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b061" target="_blank">61</a>], 2lbd for RARγ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b062" target="_blank">62</a>], 1uhl for LXRα [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b063" target="_blank">63</a>], 1pld for LXRβ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b064" target="_blank">64</a>], 1ot7 for FXR [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b065" target="_blank">65</a>], 1l2i for ERα [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b021" target="_blank">21</a>], 1qkm for ERβ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b066" target="_blank">66</a>], 2h79 for TRα[<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b067" target="_blank">67</a>], and 1q4x for TRβ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b068" target="_blank">68</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060227#pbio-0060227-b069" target="_blank">69</a>].