alexa Identification of an allosteric binding site for Zn2+ on the beta2 adrenergic receptor.


Biochemistry & Physiology: Open Access

Author(s): Swaminath G, Lee TW, Kobilka B

Abstract Share this page

Abstract The activity of G protein-coupled receptors (GPCRs) can be modulated by a diverse spectrum of drugs ranging from full agonists to partial agonists, antagonists, and inverse agonists. The vast majority of these ligands compete with native ligands for binding to orthosteric binding sites. Allosteric ligands have also been described for a number of GPCRs. However, little is known about the mechanism by which these ligands modulate the affinity of receptors for orthosteric ligands. We have previously reported that Zn(II) acts as a positive allosteric modulator of the beta(2)-adrenergic receptor (beta(2)AR). To identify the Zn(2+) binding site responsible for the enhancement of agonist affinity in the beta(2)AR, we mutated histidines located in hydrophilic sequences bridging the seven transmembrane domains. Mutation of His-269 abolished the effect of Zn(2+) on agonist affinity. Mutations of other histidines had no effect on agonist affinity. Further mutagenesis of residues adjacent to His-269 demonstrated that Cys-265 and Glu-225 are also required to achieve the full allosteric effect of Zn(2+) on agonist binding. Our results suggest that bridging of the cytoplasmic extensions of TM5 and TM6 by Zn(2+) facilitates agonist binding. These results are in agreement with recent biophysical studies demonstrating that agonist binding leads to movement of TM6 relative to TM5. This article was published in J Biol Chem and referenced in Biochemistry & Physiology: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 9th International Conference on Structural Biology
    September 18-20, 2017 Zurich, Switzerland

  •  2nd International Conference on Biochemistry
    Sep 21-22, 2017, Macau, Hong Kong
  • 2nd International Conference on Biochemistry
    September 28-29, 2017 Dubai, UAE

  • 3rd Annual Congress on Bioscience
    October 16-17, 2017 Dubai,UAE

  • 3rd International Conference on Transcriptomics
    October 30 - November 01, 2017 Bangkok, Thailand

  • 3rd International Conference on Genetic and Protein Engineering (10 Plenary Forums - 1 Event)
    November 08-09, 2017 Las Vegas, USA

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version