Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy

Journal of Magnetic Resonance
Naoki KimataSteven O Smith

Abstract

G protein-coupled receptors (GPCRs) span cell membranes with seven transmembrane helices and respond to a diverse array of extracellular signals. Crystal structures of GPCRs have provided key insights into the architecture of these receptors and the role of conserved residues. However, the question of how ligand binding induces the conformational changes that are essential for activation remains largely unanswered. Since the extracellular sequences and structures of GPCRs are not conserved between receptor subfamilies, it is likely that the initial molecular triggers for activation vary depending on the specific type of ligand and receptor. In this article, we describe NMR studies on the rhodopsin subfamily of GPCRs and propose a mechanism for how retinal isomerization switches the receptor to the active conformation. These results suggest a general approach for determining the triggers for activation in other GPCR subfamilies using NMR spectroscopy.

References

Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·D W CorsonK Nakanishi
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·P J ReevesH G Khorana
Dec 13, 1996·The Journal of Biological Chemistry·M HanT P Sakmar
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·M HanS O Smith
Aug 5, 2000·Science·K PalczewskiM Miyano
Aug 15, 2001·The Journal of Biological Chemistry·R Vogel, F Siebert
Apr 20, 2002·Biophysical Journal·Markus EilersSteven O Smith
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Philip J ReevesH Gobind Khorana
Mar 17, 2004·Journal of Molecular Biology·Wei LiuSteven O Smith
Aug 26, 2004·Journal of Molecular Biology·Tetsuji OkadaVolker Buss
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·Thue W SchwartzChristian E Elling
Mar 29, 2006·The Journal of Biological Chemistry·Christian E EllingThue W Schwartz
Mar 14, 2007·Journal of Structural Biology·Christian KlammtFrank Bernhard
Jul 17, 2007·Trends in Pharmacological Sciences·Brian K Kobilka, Xavier Deupi
Nov 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Mohana MahalingamReiner Vogel
Jan 30, 2009·The Journal of Biological Chemistry·Shivani AhujaSteven O Smith
Feb 3, 2009·Nature Structural & Molecular Biology·Shivani AhujaMarkus Eilers
Sep 8, 2009·Trends in Pharmacological Sciences·Shivani Ahuja, Steven O Smith
Dec 24, 2009·Current Pharmaceutical Design·Irina G Tikhonova, Stefano Costanzi
Mar 3, 2010·Annual Review of Biophysics·Steven O Smith
Mar 12, 2011·Science·Fei XuRaymond C Stevens
Jul 5, 2011·Current Opinion in Structural Biology·Xavier Deupi, Jörg Standfuss
Dec 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xavier DeupiJörg Standfuss
Feb 22, 2012·Science·Michael A HansonRaymond C Stevens
Nov 9, 2012·The Journal of Biological Chemistry·Louise Valentin-HansenThue W Schwartz

❮ Previous
Next ❯

Citations

Sep 24, 2016·Quarterly Reviews of Biophysics·Mohammed KaplanMarc Baldus
Nov 9, 2016·Frontiers in Physiology·Stefan Gahbauer, Rainer A Böckmann
May 27, 2017·Protein Science : a Publication of the Protein Society·Reinhard Grisshammer
Jun 9, 2016·Nature Structural & Molecular Biology·Binyong Liang, Lukas K Tamm
Dec 1, 2018·Journal of Molecular Modeling·Christian A SöldnerHeinrich Sticht

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Trends in Pharmacological Sciences
Shivani Ahuja, Steven O Smith
Current Opinion in Structural Biology
William I Weis, Brian Kobilka
Trends in Endocrinology and Metabolism : TEM
Sadashiva S KarnikTakanobu Takezako
© 2021 Meta ULC. All rights reserved