Abstract
The highly constitutively active G protein-coupled receptor US28 of human cytomegalovirus (HCMV) is thought to camouflage agonism by mediating constitutive endocytosis. With the use of the US28Δ300 mutant, which is largely devoid of constitutive internalization, I have demonstrated that the coupling of the receptor to its downstream signaling partners is responsible for the inverse agonism to agonism efficacy switch in some small-weight ligands of US28.
Keywords:
Allosteric modulation; Efficacy switch; G protein-coupled receptor; Human cytomegalovirus; Inverse agonism; US28.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation / drug effects
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Chemokine CCL5 / chemistry
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Chemokine CCL5 / pharmacology*
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Chemokine CX3CL1 / chemistry
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Chemokine CX3CL1 / pharmacology*
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Dose-Response Relationship, Drug
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HEK293 Cells
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Humans
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Ligands
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Molecular Structure
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Molecular Weight
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Piperidines / chemistry
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Piperidines / pharmacology*
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Receptors, Chemokine / agonists*
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Receptors, Chemokine / genetics
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Structure-Activity Relationship
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Viral Proteins / agonists*
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Viral Proteins / genetics
Substances
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Chemokine CCL5
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Chemokine CX3CL1
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Ligands
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Piperidines
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Receptors, Chemokine
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US28 receptor, Cytomegalovirus
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VUF 2274
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Viral Proteins