ArticleThe Journal of biological chemistry2011
From molecular details of the interplay between transmembrane helices of the thyrotropin receptor to general aspects of signal transduction in family a G-protein-coupled receptors (GPCRs).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Recombinant expression and preliminary characterization of Peptidyl-prolyl cis/trans-isomerase Rrd1 from Saccharomyces cerevisiae.PloS one · 2023Article
- Discovery of a Positive Allosteric Modulator of the Thyrotropin Receptor: Potentiation of Thyrotropin-Mediated Preosteoblast Differentiation In Vitro.The Journal of pharmacology and experimental therapeutics · 2018Article
- Structure and activation of the TSH receptor transmembrane domain.Auto- immunity highlights · 2017Article
- GPCR-SSFE 2.0-a fragment-based molecular modeling web tool for Class A G-protein coupled receptors.Nucleic acids research · 2017Article
- Structural-Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work.Frontiers in endocrinology · 2017Review
- Minireview: Insights Into the Structural and Molecular Consequences of the TSH-β Mutation C105Vfs114X.Molecular endocrinology (Baltimore, Md.) · 2016Review
- In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.Environmental health perspectives · 2016Article
- The Activation Mechanism of Glycoprotein Hormone Receptors with Implications in the Cause and Therapy of Endocrine Diseases.The Journal of biological chemistry · 2016Article
- An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.Frontiers in endocrinology · 2016Article
- Article
- New small molecule agonists to the thyrotropin receptor.Thyroid : official journal of the American Thyroid Association · 2015Article
- Novel insights on thyroid-stimulating hormone receptor signal transduction.Endocrine reviews · 2013Review
- Probing the interaction of SR141716A with the CB1 receptor.The Journal of biological chemistry · 2012Article
- Article
- Mutually opposite signal modulation by hypothalamic heterodimerization of ghrelin and melanocortin-3 receptors.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transmembrane helices (TMHs) 5 and 6 are known to be important for signal transduction by G-protein-coupled receptors (GPCRs). Our aim was to characterize the interface between TMH5 and TMH6 of the thyrotropin receptor (TSHR) to gain molecular insights into aspects of signal transduction and regulation. A proline at TMH5 position 5.50 is highly conserved in family A GPCRs and causes a twist in the helix structure. Mutation of the TSHR-specific alanine (Ala-593⁵·⁵⁰) at this position to proline resulted in a 20-fold reduction of cell surface expression. This indicates that TMH5 in the TSHR might have a conformation different from most other family A GPCRs by forming a regular α-helix. Furthermore, linking our own and previous data from directed mutagenesis with structural information led to suggestions of distinct pairs of interacting residues between TMH5 and TMH6 that are responsible for stabilizing either the basal or the active state. Our insights suggest that the inactive state conformation is constrained by a core set of polar interactions among TMHs 2, 3, 6, and 7 and in contrast that the active state conformation is stabilized mainly by non-polar interactions between TMHs 5 and 6. Our findings might be relevant for all family A GPCRs as supported by a statistical analysis of residue properties between the TMHs of a vast number of GPCR sequences.
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