scholarly journals Glutamate Binding and Conformational Flexibility of Ligand-binding Domains Are Critical Early Determinants of Efficient Kainate Receptor Biogenesis

2009 ◽  
Vol 284 (21) ◽  
pp. 14503-14512 ◽  
Author(s):  
Martin B. Gill ◽  
Pornpun Vivithanaporn ◽  
Geoffrey T. Swanson
Keyword(s):  
Ligand Binding ◽  
Conformational Flexibility ◽  
Kainate Receptor ◽  
Binding Domains ◽  
Glutamate Binding

scholarly journals Architecture and structural dynamics of the heteromeric GluK2/K5 kainate receptor

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Nandish Khanra ◽  
Patricia MGE Brown ◽  
Amanda M Perozzo ◽  
Derek Bowie ◽  
Joel Meyerson
Keyword(s):  
Ligand Binding ◽  
Structural Dynamics ◽  
Kainate Receptors ◽  
Kainate Receptor ◽  
Assembly Rules ◽  
Structural Rearrangements ◽  
Closed Channel ◽  
Binding Domains ◽  
The Brain ◽  
Channel Structures

Kainate receptors (KARs) are L-glutamate-gated ion channels that regulate synaptic transmission and modulate neuronal circuits. KARs have strict assembly rules and primarily function as heteromeric receptors in the brain. A longstanding question is how KAR heteromer subunits organize and coordinate together to fulfill their signature physiological roles. Here we report structures of the GluK2/GluK5 heteromer in apo, antagonist-bound, and desensitized states. The receptor assembles with two copies of each subunit, ligand binding domains arranged as two heterodimers, and GluK5 subunits proximal to the channel. Strikingly, during desensitization GluK2 but not GluK5 subunits undergo major structural rearrangements to facilitate channel closure. We show how the large conformational differences between antagonist-bound and desensitized states are mediated by the linkers connecting the pore helices to the ligand-binding domains. This work presents the first KAR heteromer structure, reveals how its subunits are organized, and resolves how the heteromer can accommodate functionally-distinct closed channel structures.

Unprecedented conformational flexibility revealed in the ligand-binding domains of theBovicola ovisecdysone receptor (EcR) and ultraspiracle (USP) subunits

2014 ◽  
Vol 70 (7) ◽  
pp. 1954-1964 ◽  
Author(s):  
Bin Ren ◽  
Thomas S. Peat ◽  
Victor A. Streltsov ◽  
Matthew Pollard ◽  
Ross Fernley ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Pocket ◽  
Conformational Flexibility ◽  
Order Structure ◽  
Ecdysone Receptor ◽  
Binding Region ◽  
X Ray ◽  
Receptor Structure ◽  
Binding Domains ◽  
Crystallographic Structures

The heterodimeric ligand-binding region of theBovicola ovisecdysone receptor has been crystallized either in the presence of an ecdysteroid or a synthetic methylene lactam insecticide. Two X-ray crystallographic structures, determined at 2.7 Å resolution, show that the ligand-binding domains of both subunits of this receptor, like those of other nuclear receptors, can display significant conformational flexibility. Thermal melt experiments show that while ponasterone A stabilizes the higher order structure of the heterodimer in solution, the methylene lactam destabilizes it. The conformations of the EcR and USP subunits observed in the structure crystallized in the presence of the methylene lactam have not been seen previously in any ecdysone receptor structure and represent a new level of conformational flexibility for these important receptors. Interestingly, the new USP conformation presents an open, unoccupied ligand-binding pocket.

scholarly journals Paired opposing leukocyte receptors recognizing rapidly evolving ligands are subject to homogenization of their ligand binding domains

2011 ◽  
Vol 63 (12) ◽  
pp. 809-820 ◽  
Author(s):  
Sigbjørn Fossum ◽  
Per Christian Saether ◽  
John Torgils Vaage ◽  
Michael Rory Daws ◽  
Erik Dissen
Keyword(s):  
Ligand Binding ◽  
Binding Domains ◽  
Leukocyte Receptors

scholarly journals Structure And Stability Of Ligand Binding Core Dimer Assembly Controls Desensitization In A Kainate Receptor

2009 ◽  
Vol 96 (3) ◽  
pp. 491a
Author(s):  
Charu Chaudhry ◽  
Matthew C. Weston ◽  
Peter Schuck ◽  
Christian Rosenmund ◽  
Mark L. Mayer
Keyword(s):  
Ligand Binding ◽  
Kainate Receptor ◽  
Structure And Stability ◽  
Binding Core

scholarly journals Biochemical and NMR Mapping of the Interface between CREB-binding Protein and Ligand Binding Domains of Nuclear Receptor

2004 ◽  
Vol 280 (7) ◽  
pp. 5682-5692 ◽  
Author(s):  
Fabrice A. C. Klein ◽  
R. Andrew Atkinson ◽  
Noelle Potier ◽  
Dino Moras ◽  
Jean Cavarelli
Keyword(s):  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Binding Domains

Ligand modulates the conversion of DNA-bound vitamin D3 receptor (VDR) homodimers into VDR-retinoid X receptor heterodimers

1994 ◽  
Vol 14 (5) ◽  
pp. 3329-3338
Author(s):  
B Cheskis ◽  
L P Freedman
Keyword(s):  
Ligand Binding ◽  
Vitamin D3 ◽  
Hormone Receptors ◽  
Steroid Receptors ◽  
Dependent Manner ◽  
D3 Receptor ◽  
Vitamin D3 Receptor ◽  
Binding Domains

Protein dimerization facilitates cooperative, high-affinity interactions with DNA. Nuclear hormone receptors, for example, bind either as homodimers or as heterodimers with retinoid X receptors (RXR) to half-site repeats that are stabilized by protein-protein interactions mediated by residues within both the DNA- and ligand-binding domains. In vivo, ligand binding among the subfamily of steroid receptors unmasks the nuclear localization and DNA-binding domains from a complex with auxiliary factors such as the heat shock proteins. However, the role of ligand is less clear among nuclear receptors, since they are constitutively localized to the nucleus and are presumably associated with DNA in the absence of ligand. In this study, we have begun to explore the role of the ligand in vitamin D3 receptor (VDR) function by examining its effect on receptor homodimer and heterodimer formation. Our results demonstrate that VDR is a monomer in solution; VDR binding to a specific DNA element leads to the formation of a homodimeric complex through a monomeric intermediate. We find that 1,25-dihydroxyvitamin D3, the ligand for VDR, decreases the amount of the DNA-bound VDR homodimer complex. It does so by significantly decreasing the rate of conversion of DNA-bound monomer to homodimer and at the same time enhancing the dissociation of the dimeric complex. This effectively stabilizes the bound monomeric species, which in turn serves to favor the formation of a VDR-RXR heterodimer. The ligand for RXR, 9-cis retinoic acid, has the opposite effect of destabilizing the heterodimeric-DNA complex. These results may explain how a nuclear receptor can bind DNA constitutively but still act to regulate transcription in a fully hormone-dependent manner.

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