Ice breaking in GPCR structural biology

Zhao, Qiang; Wu, Beili

doi:10.1038/aps.2011.187

Cited by 43 publications

(28 citation statements)

References 91 publications

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“…This architecture is confirmed by the inspection of solved GPCR structures (reviewed in Kobilka & Schertler 2008, Hanson & Stevens 2009, Lodowski et al 2009). As a result of advanced experimental methods (Tate & Schertler 2009), many GPCR crystal structures have been published in the last decade (Zhao & Wu 2012, Piscitelli et al 2015 and are useful tools to improve pharmacological approaches directed to GPCRs (Carlsson et al 2011, Kontoyianni & Liu 2012, Mason et al 2012, Shoichet & Kobilka 2012.…”

Section: How Do Gpcrs Function?mentioning

confidence: 99%

Oligomerization of GPCRs involved in endocrine regulation

Kleinau¹,

Müller²,

Biebermann³

2016

J Mol Endocrinol

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Section: How Do Gpcrs Function?mentioning

confidence: 99%

Oligomerization of GPCRs involved in endocrine regulation

Kleinau¹,

Müller²,

Biebermann³

2016

J Mol Endocrinol

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“…A large number of GPCR crystal structures in different activity-state-related conformations have been published in recent years (Zhao and Wu, 2012), most of them cocrystallized with specific ligands (agonists or antagonists) (Kobilka and Schertler, 2008;Hanson and Stevens, 2009). Therefore, they serve as optimal templates for family A GPCR homology modeling (OTRs are members of family A GPCRs) with the purpose to study potential details of ligand binding or signal transduction.…”

mentioning

confidence: 99%

Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors

Busnelli

Bulgheroni

Manning

et al. 2013

J Pharmacol Exp Ther

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The neuropeptides oxytocin (OT) and vasopressin (AVP) have been shown to play a central role in social behaviors; as a consequence, they have been recognized as potential drugs to treat neurodevelopmental and psychiatric disorders characterized by impaired social interactions. However, despite the basic and preclinical relevance of mouse strains carrying genetic alterations in the OT/AVP systems to basic and preclinical translational neuroscience, the pharmacological profile of mouse OT/AVP receptor subtypes has not been fully characterized. To fill in this gap, we have characterized a number of OT and AVP agonists and antagonists at three murine OT/AVP receptors expressed in the nervous system as follows: the oxytocin (mOTR) and vasopressin V1a (mV1aR) and V1b (mV1bR) subtypes. These three receptors were transiently expressed in vitro for binding and intracellular signaling assays, and then a homology model of the mOTR structure was constructed to investigate how its molecular features compare with human and rat OTR orthologs. Our data indicate that the selectivity profile of the natural ligands, OT and AVP, is conserved in humans, rats, and mice. Furthermore, we found that the synthetic peptide [Thr 4 Gly 7 ]OT (TGOT) is remarkably selective for the mOTR and, like the endogenous OT ligand, activates G q and G i and recruits b-arrestins. Finally, we report three antagonists that exhibit remarkably high affinities and selectivities at mOTRs. These highly selective pharmacological tools will contribute to the investigation of the specific physiologic and pathologic roles of mOTR for the development of selective OT-based therapeutics.

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“…27 Detergents may be used to maintain folding of the receptor, but this approach presents its own issues as the detergents that may be required to stabilize the receptor could potentially mask accessible epitopes. 28 Heterogeneity in GPCRs presents an additional challenge. The receptors are dynamic structures that exist in multiple conformations unless constrained by a stabilizing ligand.…”

Section: Introductionmentioning

confidence: 99%