Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

A Surface-Exposed Region of Gsα in Which Substitutions Decrease Receptor-Mediated Activation and Increase Receptor Affinity

Galina Grishina and Catherine H. Berlot
Molecular Pharmacology June 2000, 57 (6) 1081-1092;
Galina Grishina
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine H. Berlot
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The mechanism by which receptors activate G proteins is unclear because a connection between the receptor and the nucleotide binding site has not been established. To investigate this mechanism, we evaluated the roles in receptor interaction of three potential receptor contact sites in αs: the α2/β4, α3/β5, and α4/β6 loops. Substitutions of αi2 homologs for αsresidues in the α2/β4 loop and alanine substitutions of residues in the α4/β6 loop do not affect activation by the β2-adrenergic receptor. However, replacement of five αs residues in the α3/β5 loop region with the homologous αi2 residues decreases receptor-mediated activation of αs and increases the affinity of Gs for this receptor. The substitutions do not alter guanine nucleotide binding or hydrolysis, or activation by aluminum fluoride, indicating that the effects on receptor interaction are not due to a destabilization of the guanine-nucleotide bound state. In a model of the receptor-G protein complex, the α3/β5 loop maps near the second and third intracellular loops of the receptor. The effects of the α3/β5 substitutions suggest that the wild-type residues may be receptor contact sites that are optimized to ensure the reversibility of receptor-G protein interactions. Furthermore, the α3/β5 region corresponds to an exchange factor contact site in both EF-Tu and Ras, suggesting that the mechanisms by which seven-transmembrane receptors and exchange factors catalyze nucleotide exchange may share common elements.

Footnotes

  • Send reprint requests to: Dr. Catherine H. Berlot, Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8026. E-mail:catherine.berlot{at}yale.edu

  • This work was supported by National Institutes of Health Grant GM50369 (C.H.B.) C.H.B. is an Established Investigator of the American Heart Association.

  • ↵1 Residue numbering throughout is according to the long splice variant of αs.

  • ↵2 The αs residue 354 is not shown because it represents an insertion of sequence relative to that of the αt/αi1 chimera in the model.

  • Abbreviations:
    GTPγS
    guanosine 5′-O-(3-thiotriphosphate)
    ICYP
    iodocyanopindolol
    DTT
    dithiothreitol
    • Received November 9, 1999.
    • Accepted February 10, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 57 (6)
Molecular Pharmacology
Vol. 57, Issue 6
1 Jun 2000
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
A Surface-Exposed Region of Gsα in Which Substitutions Decrease Receptor-Mediated Activation and Increase Receptor Affinity
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

A Surface-Exposed Region of Gsα in Which Substitutions Decrease Receptor-Mediated Activation and Increase Receptor Affinity

Galina Grishina and Catherine H. Berlot
Molecular Pharmacology June 1, 2000, 57 (6) 1081-1092;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

A Surface-Exposed Region of Gsα in Which Substitutions Decrease Receptor-Mediated Activation and Increase Receptor Affinity

Galina Grishina and Catherine H. Berlot
Molecular Pharmacology June 1, 2000, 57 (6) 1081-1092;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Nelfinavir and PXR
  • P2X7 Positive Modulator Structure-Activity Relationship
  • Predicting Drug Interactions with ENT1 and ENT2
Show more Article

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics