1zdu
From Proteopedia
(New page: 200px<br /> <applet load="1zdu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zdu, resolution 2.50Å" /> '''The Crystal Structu...) |
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| - | [[Image:1zdu.gif|left|200px]]<br /> | + | [[Image:1zdu.gif|left|200px]]<br /><applet load="1zdu" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zdu" size=" | + | |
caption="1zdu, resolution 2.50Å" /> | caption="1zdu, resolution 2.50Å" /> | ||
'''The Crystal Structure of Human Liver Receptor Homologue-1'''<br /> | '''The Crystal Structure of Human Liver Receptor Homologue-1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) | + | Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a critical factor for development of endodermal tissues and regulates cholesterol and bile acid homeostasis. Regulatory ligands are unknown for SF-1 and LRH-1. A reported mouse LRH-1 structure revealed an empty pocket in a region commonly occupied by ligands in the structures of other nuclear receptors, and pocket-filling mutations did not alter the constitutive activity observed. Here we report the crystal structures of the putative ligand-binding domains of human SF-1 at 2.1-A resolution and human LRH-1 at 2.5-A resolution. Both structures bind a coactivator-derived peptide at the canonical activation-function surface, thus adopting the transcriptionally activating conformation. In human LRH-1, coactivator peptide binding also occurs to a second site. We discovered in both structures a phospholipid molecule bound in a pocket of the putative ligand-binding domain. MS analysis of the protein samples used for crystallization indicated that the two proteins associate with a range of phospholipids. Mutations of the pocket-lining residues reduced the transcriptional activities of SF-1 and LRH-1 in mammalian cell transfection assays without affecting their expression levels. These results suggest that human SF-1 and LRH-1 may be ligand-binding receptors, although it remains to be seen if phospholipids or possibly other molecules regulate SF-1 or LRH-1 under physiological conditions. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZDU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with P3A and TRS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1ZDU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=P3A:'>P3A</scene> and <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Eng, K.]] | [[Category: Eng, K.]] | ||
| - | [[Category: Krupka, H | + | [[Category: Krupka, H I.]] |
[[Category: Marimuthu, A.]] | [[Category: Marimuthu, A.]] | ||
[[Category: Mehra, U.]] | [[Category: Mehra, U.]] | ||
| - | [[Category: Milburn, M | + | [[Category: Milburn, M V.]] |
[[Category: Nguyen, H.]] | [[Category: Nguyen, H.]] | ||
[[Category: Powell, B.]] | [[Category: Powell, B.]] | ||
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[[Category: Tabrizizad, M.]] | [[Category: Tabrizizad, M.]] | ||
[[Category: Wang, W.]] | [[Category: Wang, W.]] | ||
| - | [[Category: West, B | + | [[Category: West, B L.]] |
[[Category: Zhang, C.]] | [[Category: Zhang, C.]] | ||
[[Category: P3A]] | [[Category: P3A]] | ||
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[[Category: phospholipid]] | [[Category: phospholipid]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:36 2008'' |
Revision as of 14:14, 21 February 2008
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The Crystal Structure of Human Liver Receptor Homologue-1
Overview
Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a critical factor for development of endodermal tissues and regulates cholesterol and bile acid homeostasis. Regulatory ligands are unknown for SF-1 and LRH-1. A reported mouse LRH-1 structure revealed an empty pocket in a region commonly occupied by ligands in the structures of other nuclear receptors, and pocket-filling mutations did not alter the constitutive activity observed. Here we report the crystal structures of the putative ligand-binding domains of human SF-1 at 2.1-A resolution and human LRH-1 at 2.5-A resolution. Both structures bind a coactivator-derived peptide at the canonical activation-function surface, thus adopting the transcriptionally activating conformation. In human LRH-1, coactivator peptide binding also occurs to a second site. We discovered in both structures a phospholipid molecule bound in a pocket of the putative ligand-binding domain. MS analysis of the protein samples used for crystallization indicated that the two proteins associate with a range of phospholipids. Mutations of the pocket-lining residues reduced the transcriptional activities of SF-1 and LRH-1 in mammalian cell transfection assays without affecting their expression levels. These results suggest that human SF-1 and LRH-1 may be ligand-binding receptors, although it remains to be seen if phospholipids or possibly other molecules regulate SF-1 or LRH-1 under physiological conditions.
About this Structure
1ZDU is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1., Wang W, Zhang C, Marimuthu A, Krupka HI, Tabrizizad M, Shelloe R, Mehra U, Eng K, Nguyen H, Settachatgul C, Powell B, Milburn MV, West BL, Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10. Epub 2005 May 16. PMID:15897460
Page seeded by OCA on Thu Feb 21 16:14:36 2008
Categories: Homo sapiens | Protein complex | Eng, K. | Krupka, H I. | Marimuthu, A. | Mehra, U. | Milburn, M V. | Nguyen, H. | Powell, B. | Settachatgul, C. | Shelloe, R. | Tabrizizad, M. | Wang, W. | West, B L. | Zhang, C. | P3A | TRS | Liver receptor homologue-1 | Lrh-1 | Nuclear receptor | Phosphatidylethanolamine | Phospholipid
