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Conformational Entropic Maps of Functional Coupling Domains in GPCR Activation: A Case Study of β2 Adrenergic Receptor

Liu, Fan and Abrol, Ravinder and Goddard, William A., III and Dougherty, Dennis A. (2013) Conformational Entropic Maps of Functional Coupling Domains in GPCR Activation: A Case Study of β2 Adrenergic Receptor. Biophysical Journal, 104 (2). 537A. ISSN 0006-3495. doi:10.1016/j.bpj.2012.11.2975. https://resolver.caltech.edu/CaltechAUTHORS:20130425-132232077

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Abstract

Enthalpic and entropic changes during GPCR activation are poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several 'local activating switches' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain composed of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from molecular dynamics simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm in terms of receptor entropic maps provides a novel way to design functionally biased mutants and may also assist in the identification of allosteric sites in GPCRs.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.bpj.2012.11.2975DOIAbstract
http://www.sciencedirect.com/science/article/pii/S000634951204221XPublisherAbstract
ORCID:
AuthorORCID
Abrol, Ravinder0000-0001-7333-6793
Goddard, William A., III0000-0003-0097-5716
Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 2013 Biophysical Society. Published by Elsevier Inc.
Issue or Number:2
DOI:10.1016/j.bpj.2012.11.2975
Record Number:CaltechAUTHORS:20130425-132232077
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130425-132232077
Official Citation:Fan Liu, Ravinder Abrol, William A. Goddard III, Dennis A. Dougherty, Conformational Entropic Maps of Functional Coupling Domains in GPCR Activation: A Case Study of β2 Adrenergic Receptor, Biophysical Journal, Volume 104, Issue 2, Supplement 1, 29 January 2013, Page 537a, ISSN 0006-3495, 10.1016/j.bpj.2012.11.2975.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:38119
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 May 2013 21:43
Last Modified:09 Nov 2021 23:33

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