Conformational Entropic Maps of Functional Coupling Domains in GPCR Activation: A Case Study of β2 Adrenergic Receptor
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.
Additional Information
© 2013 Biophysical Society. Published by Elsevier Inc.Attached Files
Published - 1-s2.0-S000634951204221X-main.pdf
Files
Name | Size | Download all |
---|---|---|
md5:ef59692bf8b890b76fbe6f0b86c3346a
|
38.9 kB | Preview Download |
Additional details
- Eprint ID
- 38119
- Resolver ID
- CaltechAUTHORS:20130425-132232077
- Created
-
2013-05-03Created from EPrint's datestamp field
- Updated
-
2021-11-09Created from EPrint's last_modified field