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Cell Signaling – GPCRs

[3D concept art of G-protein coupled receptors] (April 27, 2019) https://theskepticalchemist.com/gpcrs-drug-discovery/

Introduction

Cell signaling is the communication of cells by releasing, receiving, and responding to chemical signals. (Libretexts, & Harris, K. (2020, July 14). Signal Transduction. Biology LibreTexts. https://bio.libretexts.org/Learning_Objects/Worksheets/Biology_Tutorials/Signal_Transduction)

By emitting molecules into extracellular space, cells give out information and commands that are essential for the survival of our cells and body, such as cell proliferation. Cells can give out signals to themselves (autocrine), to nearby cells (paracrine), and faraway cells (endocrine). (Lumen Learning. (n.d.). Signaling Molecules and Cellular Receptors | Boundless Biology. Lumen Learning – Boundless Biology. https://courses.lumenlearning.com/boundless-biology/chapter/signaling-molecules-and-cellular-receptors/)

The signaling cascade is separated into 3 stages. First, the cell receive the signal molecules (ligands) by binding to receptors. Next, the structure of the receptor proteins change as the signal molecules bind to the receptors, which triggers other relay molecules in the cell to pass down the original signal. This is known as the signal transduction. Finally, the cell responds to the signal. In many cases, cell signaling results in the activation (or deactivation) of gene expression. The cell might undergo apoptosis, the death of cells, or cell division as an outcome of cell division. 

(Libretexts. (2020, July 14). Signal Transduction. Biology LibreTexts. https://bio.libretexts.org/Learning_Objects/Worksheets/Biology_Tutorials/Signal_Transduction)

There are three main types of cell-surface receptors found in different cells: the G-protein coupled receptor (GPCR), ion channel receptors, and enzyme-linked receptors. In this article, we will be focusing on the GPCRs.

G-protein coupled receptors are found throughout human tissue cells, and responds to many important stimulus, like hormones and neurotransmitters (Teach Me. (2021, August 26). G-Proteins – Receptors – Structure – Function. TeachMePhysiology. https://teachmephysiology.com/biochemistry/molecules-and-signalling/g-protein/). GPCRs have a molecule-binding site outside the cell membrane, 7 transmembrane domains, and a G-protein composed of 3 subunits in the intercellular space – α, β and γ.  (Miller EJ, Lappin SL. Physiology, Cellular Receptor. [Updated 2021 Apr 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554403/). While different GPCRs have identical transmembrane domains, their extracellular and G-protein domains are specific (Lumen Learning. (n.d.). Signaling Molecules and Cellular Receptors | Boundless Biology. Lumen Learning – Boundless Biology. https://courses.lumenlearning.com/boundless-biology/chapter/signaling-molecules-and-cellular-receptors/

When no ligands are present, the α subunit is connected to a GDP, and are attached to β and γ that are linked to the cell membrane by a lipid anchor. As ligands bind to the extracellular domain of the GPCRs, conformational shape changes occur for the GPCRs, resulting in the release of GDP from the α subunit. GTP replaces the released GDP, causing the separation of α and GTP from the transmembrane domain and the βγ-subunit. This allows the α-subunit and the βγ-subunit to bind to according effector molecules – a molecule that binds to a protein and affects the function of that protein – and initiate the signal transduction. (Teach Me. (2021, August 26). G-Proteins – Receptors – Structure – Function. TeachMePhysiology. https://teachmephysiology.com/biochemistry/molecules-and-signalling/g-protein/)

[ G protein structure and activation cascade] (n.d.) https://teachmephysiology.com/biochemistry/molecules-and-signalling/g-protein/
[Signaling with G-proteins] (October 2004) https://pdb101.rcsb.org/motm/58
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