1yje
From Proteopedia
(New page: 200px<br /><applet load="1yje" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yje, resolution 2.40Å" /> '''Crystal structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1yje.gif|left|200px]]<br /><applet load="1yje" size=" | + | [[Image:1yje.gif|left|200px]]<br /><applet load="1yje" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1yje, resolution 2.40Å" /> | caption="1yje, resolution 2.40Å" /> | ||
'''Crystal structure of the rNGFI-B ligand-binding domain'''<br /> | '''Crystal structure of the rNGFI-B ligand-binding domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | NGFI-B is a ligand-independent orphan nuclear receptor of the NR4A | + | NGFI-B is a ligand-independent orphan nuclear receptor of the NR4A subfamily that displays important functional differences with its homolog Nurr1. In particular, the NGFI-B ligand-binding domain (LBD) exhibits only modest activity in cell lines in which the Nurr1 LBD strongly activates transcription. To gain insight into the structural basis for the distinct activation potentials, we determined the crystal structure of the NGFI-B LBD at 2.4-angstroms resolution. Superimposition with the Nurr1 LBD revealed a significant shift of the position of helix 12, potentially caused by conservative amino acids exchanges in helix 3 or helix 12. Replacement of the helix 11-12 region of Nurr1 with that of NGFI-B dramatically reduces the transcriptional activity of the Nurr1 LBD. Similarly, mutation of Met414 in helix 3 to leucine or of Leu591 in helix 12 to isoleucine (the corresponding residues found in NGFI-B) significantly affects Nurr1 transactivation. In comparison, swapping the helix 11-12 region of Nurr1 into NGFI-B results in a modest increase of activity. These observations reveal a high sensitivity of LBD activity to changes that influence helix 12 positioning. Furthermore, mutation of hydrophobic surface residues in the helix 11-12 region (outside the canonical co-activator surface constituted by helices 3, 4, and 12) severely affects Nurr1 transactivation. Together, our data suggest that a novel co-regulator surface that includes helix 11 and a specifically positioned helix 12 determine the cell type-dependent activities of the NGFI-B and the Nurr1 LBD. |
==About this Structure== | ==About this Structure== | ||
| - | 1YJE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http:// | + | 1YJE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YJE OCA]. |
==Reference== | ==Reference== | ||
| Line 17: | Line 17: | ||
[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
[[Category: Peluso-Iltis, C.]] | [[Category: Peluso-Iltis, C.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: cell-specific]] | [[Category: cell-specific]] | ||
[[Category: ligand-binding domain]] | [[Category: ligand-binding domain]] | ||
| Line 28: | Line 28: | ||
[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:56 2008'' |
Revision as of 14:05, 21 February 2008
|
Crystal structure of the rNGFI-B ligand-binding domain
Overview
NGFI-B is a ligand-independent orphan nuclear receptor of the NR4A subfamily that displays important functional differences with its homolog Nurr1. In particular, the NGFI-B ligand-binding domain (LBD) exhibits only modest activity in cell lines in which the Nurr1 LBD strongly activates transcription. To gain insight into the structural basis for the distinct activation potentials, we determined the crystal structure of the NGFI-B LBD at 2.4-angstroms resolution. Superimposition with the Nurr1 LBD revealed a significant shift of the position of helix 12, potentially caused by conservative amino acids exchanges in helix 3 or helix 12. Replacement of the helix 11-12 region of Nurr1 with that of NGFI-B dramatically reduces the transcriptional activity of the Nurr1 LBD. Similarly, mutation of Met414 in helix 3 to leucine or of Leu591 in helix 12 to isoleucine (the corresponding residues found in NGFI-B) significantly affects Nurr1 transactivation. In comparison, swapping the helix 11-12 region of Nurr1 into NGFI-B results in a modest increase of activity. These observations reveal a high sensitivity of LBD activity to changes that influence helix 12 positioning. Furthermore, mutation of hydrophobic surface residues in the helix 11-12 region (outside the canonical co-activator surface constituted by helices 3, 4, and 12) severely affects Nurr1 transactivation. Together, our data suggest that a novel co-regulator surface that includes helix 11 and a specifically positioned helix 12 determine the cell type-dependent activities of the NGFI-B and the Nurr1 LBD.
About this Structure
1YJE is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for the cell-specific activities of the NGFI-B and the Nurr1 ligand-binding domain., Flaig R, Greschik H, Peluso-Iltis C, Moras D, J Biol Chem. 2005 May 13;280(19):19250-8. Epub 2005 Feb 16. PMID:15716272
Page seeded by OCA on Thu Feb 21 16:05:56 2008
Categories: Rattus norvegicus | Single protein | Flaig, R. | Greschik, H. | Moras, D. | Peluso-Iltis, C. | SPINE, Structural Proteomics in Europe. | Cell-specific | Ligand-binding domain | Ngfi-b | Novel coregulator interface | Nuclear receptor | Nur77 | Spine | Structural genomics | Structural proteomics in europe
