2nxx: Difference between revisions

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==Overview==

Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as, ubiquitous heterodimerization partners of many nuclear receptors. While it, has long been accepted that a wide range of ligands can activate, vertebrate/mollusc RXRs, the existence and necessity of specific, endogenous ligands activating RXR-USP in vivo is still matter of intense, debate. Here we report the existence of a novel type of RXR-USP with a, ligand-independent functional conformation. Our studies involved Tribolium, USP (TcUSP) as representative of most arthropod RXR-USPs, with high, sequence homology to vertebrate/mollusc RXRs. The crystal structure of the, ligand-binding domain of TcUSP was solved in the context of the functional, heterodimer with the ecdysone receptor (EcR). While EcR exhibits a, canonical ligand-bound conformation, USP adopts an original apo structure., Our functional data demonstrate that TcUSP is a constitutively silent, partner of EcR, and that none of the RXR ligands can bind and activate, TcUSP. These findings together with a phylogenetic analysis suggest that, RXR-USPs have undergone remarkable functional shifts during evolution and, give insight into receptor-ligand binding evolution and dynamics.

Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.

==About this Structure==

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[[Category: hormone/growth factor complex]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:12:17 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as, ubiquitous heterodimerization partners of many nuclear receptors. While it, has long been accepted that a wide range of ligands can activate, vertebrate/mollusc RXRs, the existence and necessity of specific, endogenous ligands activating RXR-USP in vivo is still matter of intense, debate. Here we report the existence of a novel type of RXR-USP with a, ligand-independent functional conformation. Our studies involved Tribolium, USP (TcUSP) as representative of most arthropod RXR-USPs, with high, sequence homology to vertebrate/mollusc RXRs. The crystal structure of the, ligand-binding domain of TcUSP was solved in the context of the functional, heterodimer with the ecdysone receptor (EcR). While EcR exhibits a, canonical ligand-bound conformation, USP adopts an original apo structure., Our functional data demonstrate that TcUSP is a constitutively silent, partner of EcR, and that none of the RXR ligands can bind and activate, TcUSP. These findings together with a phylogenetic analysis suggest that, RXR-USPs have undergone remarkable functional shifts during evolution and, give insight into receptor-ligand binding evolution and dynamics.
+Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.
 ==About this Structure==
@@ Line 21: / Line 21: @@
 [[Category: hormone/growth factor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:18:32 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:12:17 2008''