DOCSLIB.ORG

Introduction to Receptors (1)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Introduction to Receptors (1) Introduction to Receptors (1) a b g a b PicScience LLC © 2013 Receptors are protein molecules in the target cell or on its surface that bind ligands. Receptors, either intracellular or cell-surface, bind to specific ligands, which activate numerous cellular processes. Receptors receive chemical signals that give commands to the cell. Allow this molecule to pass Divide Key Terms integral protein: a protein molecule (or assembly of proteins) that is permanently attached to the biological membrane transcription: the synthesis of RNA under the direction of DNA Internal Receptors Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis to mediate gene expression. Gene expression is the cellular process of transforming the information in a cell’s DNA into a sequence of amino acids that ultimately forms a protein. When the ligand binds to the internal receptor, a conformational change exposes a DNA-binding site on the protein. The ligand-receptor complex moves into the nucleus, binds to specific regulatory regions of the chromosomal DNA, and promotes the initiation of transcription. Internal receptors can directly influence gene expression without having to pass the signal on to other receptors or messengers. Class 1: Intracellular receptors Can be divided into 2 general groups Nuclear and cytoplasmic Cell membrane nucleus DNA Cytoplasmic – in the cytoplasm of cell Ligand binds… Cell membrane nucleus mRNA • Receptor crosses the nucleus through a pore • Binds to DNA, enhances DNA transcription • New messenger RNA leaves nucleus Nuclear – in the nucleus of cell Ligand binds… Cell membrane nucleus mRNA • Receptor bound to DNA, enhances transcription DNA • New messenger RNA leaves nucleus Cell-Surface Receptors Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored, or integral proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types. Each cell-surface receptor has three main components: an external ligand-binding domain (extracellular domain), a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The size and extent of each of these domains vary widely, depending on the type of receptor. Cell-surface receptors are involved in most of the signaling in multicellular organisms. Class I1: Cell Surface Receptors Can be divided into several categories a b N C g a b There are three general categories of cell- surface receptors: ◦ Ion channel -linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. ◦ G-protein-linked receptors bind a ligand and activate a membrane protein called a G- protein, which then interacts with either an ion channel or an enzyme in the membrane. ◦ Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. Ligand gated Ion channels Gated ion channels form a pore through the plasma membrane that opens when the signaling molecule binds. The open pore then allows ions to flow into or out of the cell. Ligand gated Ion channels Pentamers – 5 subunits Cell membrane Ligand gated Ion channels are molecules that act like Activated or turned on keys that fit certain binding pockets by or locks on the receptor. Cell membrane Ligand gated Ion channels When the ligand binds, the subunits undergo changes opening the pore ion Cell membrane Ions such as Na+, K+, Ca+2, and Cl- then flow down their electrochemical gradient into the cell Examples of these: GABA Glycine Nicotinic acetylcholine Serotonin Glutamate G-Protein Linked Receptors G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane. All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site. G-protein coupled receptors • G-protein composed of one alpha, beta, and gamma subunit • 2 primary signaling cascades: cAMP or phosphatidylinositol pathways Cell membrane g a b • Pathway activated depends on alpha subunit type G-protein coupled receptors • When a ligand binds, the receptor changes conformation, allowing G-protein to be activated (GDP is exchanged for GTP) • G-protein dissociates from receptor then subunits from each other. Cell membrane g a GTP b GTP cAMP pathway Cell membrane g a GTP b GTP Phosphatidylinositol pathway g P a P GTP b P GTP To sarcoplasmic reticulum… 6 Major classes of these Class A (or 1) (Rhodopsin-like) Class B (or 2) (Secretin receptor family) Class C (or 3) (Metabotropic glutamate/pheromone) Class D (or 4) (Fungal mating pheromone receptors) Class E (or 5) (Cyclic AMP receptors) Class F (or 6) (Frizzled/Smoothened) Receptor tyrosine kinase • Two inactive monomers contain tyrosine (Tyr) residues • Ligand binding to the monomers leads to dimer formation Cell membrane TyrTyrTyr Tyr TyrTyrTyr Tyr TyrTyrTyr Tyr Receptor tyrosine kinase ATP molecules donate a Inactive relay proteins bind phosphate (P) to each of the to the phosphorylated tyrosines. tyrosine residues and trigger cellular responses downstream Cell membrane ATP P Tyr Tyr P ATP ATP P Tyr Tyr P ATP Tyr Tyr ATP P P ATP Examples of these: Insulin Vascular Endothelial Growth Factor (VEGF) Platelet-derived Growth Factor (PDGF) Epidermal Growth Factor (EGF) Eph • Join the cytoskeleton on the inside of the cell to the Integrins extracellular matrix on the outside. • Heterodimers of alpha and beta subunits a b Cell membrane Examples of these: Ligands in ECM – collagen, fibronectin, and laminin Important for cellular processes including: cell adhesion, cell migration, signal transduction, and cell growth/death Toll-like receptors Cell membrane nucleus • Involved in the immune response • Signals between Immune response downstream proteins result in DNA enhanced transcription of inflammatory genes Examples of these: Ligands include: Lipopolysaccharide, double-stranded RNA, flagellin, heat shock proteins Important for the innate immune response to bacterial and viral stimuli. .
Load more

Recommended publications
  • Characterisation of the Α1b-Adrenoceptor by Modeling, Dynamics and Virtual Screening Kapil Jain B.Pharm, M.S.(Pharm.)
    Characterisation of the α1B-Adrenoceptor by Modeling, Dynamics and Virtual Screening Kapil Jain B.Pharm, M.S.(Pharm.) A Thesis submitted for the degree of Master of Philosophy at The University of Queensland in 2018 Institute for Molecular Bioscience 0 Abstract G protein-coupled receptors (GPCRs) are the largest druggable class of proteins yet relatively little is known about the mechanism by which agonist binding induces the conformational changes necessary for G protein activation and intracellular signaling. Recently, the Kobilka group has shown that agonists, neutral antagonists and inverse agonists stabilise distinct extracellular surface (ECS) conformations of the β2-adrenergic receptor (AR) opening up new possibilities for allosteric drug targeting at GPCRs. The goal of this project is to extend these studies to define how the ECS conformation of the α1B-AR changes during agonist binding and develop an understanding of ligand entry and exit mechanisms that may help in the design of specific ligands with higher selectivity, efficacy and longer duration of action. Two parallel approaches were initiated to identify likely functional residues. The role of residues lining the primary binding site were predicted by online web server (Q-Site Finder) while secondary binding sites residues were predicted from molecular dynamics (MD) simulations. Predicted functionally significant residues were mutated and their function was established using FLIPR, radioligand and saturation binding assays. Despite the α1B-AR being pursued as a drug target for over last few decades, few specific agonists and antagonists are known to date. In an attempt to address this gap, we pursued ligand-based approach to find potential new leads.
    [Show full text]
  • Computational Methods for Prediction and Classification of G Protein-Coupled Receptors Khodeza Begum University of Texas at El Paso, [email protected]
    University of Texas at El Paso DigitalCommons@UTEP Open Access Theses & Dissertations 2017-01-01 Computational methods for prediction and classification of G protein-coupled receptors Khodeza Begum University of Texas at El Paso, [email protected] Follow this and additional works at: https://digitalcommons.utep.edu/open_etd Part of the Bioinformatics Commons, Computer Sciences Commons, and the Mathematics Commons Recommended Citation Begum, Khodeza, "Computational methods for prediction and classification of G protein-coupled receptors" (2017). Open Access Theses & Dissertations. 408. https://digitalcommons.utep.edu/open_etd/408 This is brought to you for free and open access by DigitalCommons@UTEP. It has been accepted for inclusion in Open Access Theses & Dissertations by an authorized administrator of DigitalCommons@UTEP. For more information, please contact [email protected]. COMPUTATIONAL METHODS FOR PREDICTION AND CLASSIFICATION OF G PROTEIN-COUPLED RECEPTORS KHODEZA BEGUM Master’s Program in Computational Science APPROVED: Ming-Ying Leung, Ph.D., Chair Rachid Skouta, Ph.D. Xiaogang Su, Ph.D. Charlotte M. Vines, Ph.D. Charles Ambler, Ph.D. Dean of the Graduate School Copyright © by Khodeza Begum 2017 COMPUTATIONAL METHODS FOR PREDICTION AND CLASSIFICATION OF G PROTEIN-COUPLED RECEPTORS by KHODEZA BEGUM, B.S. THESIS Presented to the Faculty of the Graduate School of The University of Texas at El Paso in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE COMPUTATIONAL SCIENCE PROGRAM THE UNIVERSITY OF TEXAS AT EL PASO December 2017 Acknowledgements I would first like to thank my advisor Dr. Ming-Ying Leung for the continuous support and encouragement in my study and thesis.
    [Show full text]
  • Molecular Dissection of G-Protein Coupled Receptor Signaling and Oligomerization
    MOLECULAR DISSECTION OF G-PROTEIN COUPLED RECEPTOR SIGNALING AND OLIGOMERIZATION BY MICHAEL RIZZO A Dissertation Submitted to the Graduate Faculty of WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Biology December, 2019 Winston-Salem, North Carolina Approved By: Erik C. Johnson, Ph.D. Advisor Wayne E. Pratt, Ph.D. Chair Pat C. Lord, Ph.D. Gloria K. Muday, Ph.D. Ke Zhang, Ph.D. ACKNOWLEDGEMENTS I would first like to thank my advisor, Dr. Erik Johnson, for his support, expertise, and leadership during my time in his lab. Without him, the work herein would not be possible. I would also like to thank the members of my committee, Dr. Gloria Muday, Dr. Ke Zhang, Dr. Wayne Pratt, and Dr. Pat Lord, for their guidance and advice that helped improve the quality of the research presented here. I would also like to thank members of the Johnson lab, both past and present, for being valuable colleagues and friends. I would especially like to thank Dr. Jason Braco, Dr. Jon Fisher, Dr. Jake Saunders, and Becky Perry, all of whom spent a great deal of time offering me advice, proofreading grants and manuscripts, and overall supporting me through the ups and downs of the research process. Finally, I would like to thank my family, both for instilling in me a passion for knowledge and education, and for their continued support. In particular, I would like to thank my wife Emerald – I am forever indebted to you for your support throughout this process, and I will never forget the sacrifices you made to help me get to where I am today.
    [Show full text]
  • Steven, Stacy (2012) the Pharmacology of the 5-HT2A Receptor and the Difficulty Surrounding Single Taret Models
    Steven, Stacy (2012) The pharmacology of the 5-HT2A receptor and the difficulty surrounding single taret models. MSc(R) thesis. http://theses.gla.ac.uk/3636/ Copyright and moral rights for this thesis are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Glasgow Theses Service http://theses.gla.ac.uk/ [email protected] The pharmacology of the 5-HT2A receptor and the difficulty surrounding functional studies with single target models A thesis presented for the degree of Master of Science by research Stacy Steven April 2012 Treatment of many disorders can be frequently problematic due to the relatively non selective nature of many drugs available on the market. Symptoms can be complex and expansive, often leading to symptoms representing other disorders in addition to the primary reason for treatment. In particular mental health disorders fall prey to this situation. Targeting treatment can be difficult due to the implication of receptors in more than one disorder, and more than one receptor in a single disorder. In the instance of GPCRs, receptors such as the serotonin receptors (and in particular the 5-HT2A for the interest of this research) belong to a large family of receptors, the GPCR Class A super family.
    [Show full text]
  • Insights Into Nuclear G-Protein-Coupled Receptors As Therapeutic Targets in Non-Communicable Diseases
    pharmaceuticals Review Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases Salomé Gonçalves-Monteiro 1,2, Rita Ribeiro-Oliveira 1,2, Maria Sofia Vieira-Rocha 1,2, Martin Vojtek 1,2 , Joana B. Sousa 1,2,* and Carmen Diniz 1,2,* 1 Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; [email protected] (S.G.-M.); [email protected] (R.R.-O.); [email protected] (M.S.V.-R.); [email protected] (M.V.) 2 LAQV/REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal * Correspondence: [email protected] (J.B.S.); [email protected] (C.D.) Abstract: G-protein-coupled receptors (GPCRs) comprise a large protein superfamily divided into six classes, rhodopsin-like (A), secretin receptor family (B), metabotropic glutamate (C), fungal mating pheromone receptors (D), cyclic AMP receptors (E) and frizzled (F). Until recently, GPCRs signaling was thought to emanate exclusively from the plasma membrane as a response to extracellular stimuli but several studies have challenged this view demonstrating that GPCRs can be present in intracellular localizations, including in the nuclei. A renewed interest in GPCR receptors’ superfamily emerged and intensive research occurred over recent decades, particularly regarding class A GPCRs, but some class B and C have also been explored. Nuclear GPCRs proved to be functional and capable of triggering identical and/or distinct signaling pathways associated with their counterparts on the cell surface bringing new insights into the relevance of nuclear GPCRs and highlighting the Citation: Gonçalves-Monteiro, S.; nucleus as an autonomous signaling organelle (triggered by GPCRs).
    [Show full text]
  • A REVOLUTION in the PHYSIOLOGY of the LIVING CELL FUTURE ANNUAL MEETINGS of by Gilbert N
    A REVOLUTION IN THE PHYSIOLOGY OF THE LIVING CELL FUTURE ANNUAL MEETINGS OF by Gilbert N. Ling Orig. Ed. 1992 404 pp. $64.50 THE AMERICAN SOCIETY FOR ISBN 0-89464-398-3 CELL BIOLOGY The essence of a major revolution in cell physiology -the first since the cell was recognized as the basic unit of life a century and a half ago - is presented and altemative theories are discussed in this text. Although the conventional mem- brane-pump theory is still being taught, a new theory of the living cell, called the association-induction hypothesis has been proposed. It has successfullywfthstood 1995 twenty-five years of worldwide testing and has already generated an enhancing DC diagnostic tool ofgreat power, magnetic resonance imaging (MRI).This volume is Washington, intended forteachers, students and researchers ofbiology and medicine. December 9-13 i't...a correct basic theory of cell physiology, besides its great intrinsic value in mankind's search forknowledge aboutourselves and the world we live in, willalso play a crucial role in the ultimate conquest of cancer, AIDS, and other incurable 1996 diseases.'-from the Introduction. ASCB Annual Meeting/ on Cell Biology t When ordering please add t".Ling turns cellphysiology upside down. He Sixth International Congress $5.00 first bookl$1.50 each ad- practicallyredefines the cell. He provides com- San Francisco, California ditional book to cover shipping pellingevidencefor headequacyofhis theoryn December 7-11 charges. Foreign shipping costs evidence that cannot fail to impress even the available upon request. most extreme skeptics....'- Gerald H. Pollock, _ Ph.D., Univ. ofWashington.
    [Show full text]
  • Biased Signaling of G Protein Coupled Receptors (Gpcrs): Molecular Determinants of GPCR/Transducer Selectivity and Therapeutic Potential
    Pharmacology & Therapeutics 200 (2019) 148–178 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Biased signaling of G protein coupled receptors (GPCRs): Molecular determinants of GPCR/transducer selectivity and therapeutic potential Mohammad Seyedabadi a,b, Mohammad Hossein Ghahremani c, Paul R. Albert d,⁎ a Department of Pharmacology, School of Medicine, Bushehr University of Medical Sciences, Iran b Education Development Center, Bushehr University of Medical Sciences, Iran c Department of Toxicology–Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Iran d Ottawa Hospital Research Institute, Neuroscience, University of Ottawa, Canada article info abstract Available online 8 May 2019 G protein coupled receptors (GPCRs) convey signals across membranes via interaction with G proteins. Origi- nally, an individual GPCR was thought to signal through one G protein family, comprising cognate G proteins Keywords: that mediate canonical receptor signaling. However, several deviations from canonical signaling pathways for GPCR GPCRs have been described. It is now clear that GPCRs can engage with multiple G proteins and the line between Gprotein cognate and non-cognate signaling is increasingly blurred. Furthermore, GPCRs couple to non-G protein trans- β-arrestin ducers, including β-arrestins or other scaffold proteins, to initiate additional signaling cascades. Selectivity Biased Signaling Receptor/transducer selectivity is dictated by agonist-induced receptor conformations as well as by collateral fac- Therapeutic Potential tors. In particular, ligands stabilize distinct receptor conformations to preferentially activate certain pathways, designated ‘biased signaling’. In this regard, receptor sequence alignment and mutagenesis have helped to iden- tify key receptor domains for receptor/transducer specificity.
    [Show full text]
  • 2. G-Protein-Coupled Receptors (Gpcrs) 6
    DIPLOMARBEIT / DIPLOMA THESIS Titel der Diplomarbeit / Title of the Diploma Thesis „Odorant receptors“ verfasst von / submitted by Girgis Noser angestrebter akademischer Grad / in partial fulfilment of the requirements for the degree of Magister der Pharmazie (Mag.pharm.) Wien, 2016 / Vienna, 2016 Studienkennzahl lt. Studienblatt / A 996 449 degree programme code as it appears on the student record sheet: Studienrichtung lt. Studienblatt / Gleichwertigkeit Pharmazie degree programme as it appears on the student record sheet: Betreut von / Supervisor: Univ. Prof. Mag. Dr. G. Buchbauer Contents Acknowledgement III Zusammenfassung IV Abstract V General Introduction in German 1 General Introduction in English 2 1.1 Anatomy of olfactory system 3 1.2 Olfactory Epithelium 4 1.3 The olfactory bulb (OB) 4 1.4 Olfactory sensory neuron cell structure 5 2. G-protein-coupled receptors (GPCRs) 6 2.1 G-Protein-coupled receptors, classification 7 2.2 GPCRs structure. 10 2.3 Bovine Rhodopsin model 11 2.4 GPCRs activation and signaling. 15 2.4.1 Mechanism of signaling formation. 15 2.4.2 G-protein-dependent and independent signaling pathways 18 2.4.3 Terminating the signal 18 2.4.4 Types of ligand according to biological response 18 3. Olfactory receptors (ORs) 19 3.1 ORs genes as the largest gene known superfamily in GPCRs. 19 3.2 ORs genes classification and nomenclature 21 I 3.3 ORs genes distribution 24 3.4 ORs genes expression. 24 3.5 ORs 3D structure. 25 3.6 ORs-odorant interaction. 28 3.7 Signal transduction of olfaction. 30 3.8 Combinatorial coding and olfactory pattern.
    [Show full text]
  • 7Tmrmine: a Web Server for Hierarchical Mining of 7TMR Proteins Guoqing Lu University of Nebraska at Omaha
    University of Nebraska at Omaha DigitalCommons@UNO Biology Faculty Publications Department of Biology 2009 7TMRmine: a Web server for hierarchical mining of 7TMR proteins Guoqing Lu University of Nebraska at Omaha Zhifang Wang University of Nebraska-Lincoln Alan M. Jones University of North Carolina at Chapel Hill Etsuko N. Moriyama University of Nebraska-Lincoln Follow this and additional works at: https://digitalcommons.unomaha.edu/biofacpub Part of the Biology Commons, and the Plant Sciences Commons Recommended Citation Lu, Guoqing; Wang, Zhifang; Jones, Alan M.; and Moriyama, Etsuko N., "7TMRmine: a Web server for hierarchical mining of 7TMR proteins" (2009). Biology Faculty Publications. 11. https://digitalcommons.unomaha.edu/biofacpub/11 This Article is brought to you for free and open access by the Department of Biology at DigitalCommons@UNO. It has been accepted for inclusion in Biology Faculty Publications by an authorized administrator of DigitalCommons@UNO. For more information, please contact [email protected]. BMC Genomics BioMed Central Database Open Access 7TMRmine: a Web server for hierarchical mining of 7TMR proteins Guoqing Lu1,2, Zhifang Wang3, Alan M Jones4,5 and Etsuko N Moriyama*6,7 Address: 1Department of Computer Science, University of Nebraska at Omaha, Omaha, NE 68182, USA, 2Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA, 3Department of Computer Science and Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588-0660, USA, 4Departments of Biology, University of
    [Show full text]
  • Production of an Isotopically Labelled G-Protein Coupled Receptor In
    Investigations into the production of integral membrane proteins for solid-state NMR spectroscopy By Rachel Munro A Thesis presented to The University of Guelph In partial fulfillment of requirements for the degree of Master of Science in Biophysics Guelph, Ontario, Canada © Rachel Munro, January, 2016 ABSTRACT Investigations into the production of integral membrane proteins for solid-state NMR spectroscopy Rachel Munro Advisor: Professor L. Brown University of Guelph, 2015 This study seeks to probe the challenges associated with heterologous expression and isotopic labeling of microbial rhodopsins and the GPCR adenosine receptor (2A) (A2aR) through biophysical methods including SSNMR, FTIR and Raman spectroscopy. A2aR was transformed into Pichia pastoris, which has previously been shown to be able to cost-effectively produce isotopically-labelled eukaryotic membrane proteins for SSNMR studies; however poor expression resulted in contamination as detected by both FTIR and SSNMR. Next, for Anabaena sensory rhodopsin (ASR) produced in E. coli, we investigated the effect of a full-length construct on both expression and purification. Finally, we showed that the novel biosynthetic production of an isotopically labelled retinal ligand concurrently with its apoprotein proteorhodopsin in E. coli presents a cost effective alternative to de novo synthesis. By using alternately labeled carbon sources (glycerol) we were able to verify the biosynthetic pathway for retinal and assign several new carbon resonances for proteorhodopsin-bound retinal. Acknowledgements Firstly, I would like to thank my advisor, Dr. Leonid Brown, for his guidance, patience and unwavering support over the last four years. Additional thanks belong to Dr. Vladimir Ladizhansky, for being on my advisory committee and for all his help with NMR.
    [Show full text]
  • Theoretical Modeling and Docking Studies of Silkworm Serotonin
    ics om & B te i ro o P in f f o o Sumathy et al., J Proteomics Bioinform 2012, 5:10 r l m a Journal of a n t r i c u DOI: 10.4172/jpb.1000242 s o J ISSN: 0974-276X Proteomics & Bioinformatics Research Article Article OpenOpen Access Access Theoretical Modeling and Docking Studies of Silkworm Serotonin Receptor Ramasamy Sumathy1, SK Ashwath1 and VK Gopalakrishnan2* 1Bioinformatics centre, Central Sericultural Research and Training Institute, Mysore, Karnataka, India 2Department of Biochemistry and Bioinformatics, Karpagam University, Coimbatore, Tamilnadu, India Abstract The Silkworm serotonin receptor protein is an integral membrane protein which belongs to the largest superfamily of G protein-coupled receptors that communicate signals across the cell membrane through their interaction with heterotrimeric G proteins and regulate many of the physiological processes including the regulation of feeding, aggression, mood, perception, pain, anxiety etc. Despite the importance of serotonin receptor protein its structure have not yet determined experimentally due to difficulty in crystallization. The three-dimensional structure was modelled by the MODELLER program using the template rh1A which has 33% identity. The modelled structure was validated using Procheck and Ramachandran plot. It was found that the percentage of residue lying in the most favoured regions, additionally allowed regions, generously allowed regions, disallowed regions are 93.3%, 6.4%, 0% and 0.3%, respectively and it indicates reasonably good model. The overall Procheck G-factor and overall quality factor of ERRAT graph were 0.04 and 80.759, respectively. The binding site of the serotonin receptor protein was predicted using Q-Sitefinder and the interaction studies carried out with serotonin, agonist and reveals that the seven interaction residues Asp141, Val142, Gln218, Thr227, Ser230, Phe382, Leu405 of serotonin receptor protein interact with the serotonin form three hydrogen bond.
    [Show full text]
  • 1 Differential Signaling and Gene Regulation Among
    Differential Signaling and Gene Regulation Among Three Human EP3 Prostanoid Receptor Isoforms Item Type text; Electronic Dissertation Authors Israel, Davelene Davinah Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 27/09/2021 17:55:54 Link to Item http://hdl.handle.net/10150/196148 1 DIFFERENTIAL SIGNALING AND GENE REGULATION AMONG THREE HUMAN EP3 PROSTANOID RECEPTOR ISOFORMS by Davelene Davinah Israel A Dissertation Submitted to the Faculty of the DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2008 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Davelene Davinah Israel Entitled: Differential Signaling and Gene Regulation Among Three Human EP3 Prostanoid Receptor Isoforms and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy _________________________________________________ Date: 6/4/08 John W. Regan _________________________________________________ Date: 6/4/08 John W. Bloom _________________________________________________ Date: 6/4/08 W. Daniel Stamer _________________________________________________ Date: 6/4/08 Richard R. Vaillancourt ________________________________________________ Date: Final approval and acceptance of this dissertation is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement.
    [Show full text]