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PMID: 20617813 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix.

Biochemistry ·Vol. 49 ·No. 31 ·2010-08-10 ·Pages 6771-6

Provasi D, Johnston JM, Filizola M

Abstract

Several G protein-coupled receptors (GPCRs), including opioid receptors deltaOR, muOR, and kappaOR, have been reported to form stable dimers or oligomers in lipid bilayers and cell membranes. This notion has been recently challenged by imaging data supporting a transient nature of GPCR association. Here we use umbrella sampling reconstructed free energies of deltaOR homodimers involving the fourth transmembrane helix to predict their association constant. The results of these simulations, combined with estimates of diffusion-limited association rates, suggest a short lifetime for deltaOR homodimers in the membrane, in agreement with recent trends.

MeSH Terms
Animals Computer Simulation Diffusion Half-Life Humans Membrane Proteins Protein Multimerization Protein Structure, Secondary Receptors, G-Protein-Coupled Receptors, Opioid, delta/chemistry,metabolism Thermodynamics
Chemicals
Membrane Proteins Receptors, G-Protein-Coupled Receptors, Opioid, delta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Provasi Davide
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Johnston Jennifer M
Filizola Marta
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Article Info
Journal
Biochemistry
Abbr.
Biochemistry
ISSN
1520-4995
DOI
10.1021/bi100686t
Published
2010-08-10
Pages
6771-6
Language
English
Region
United States
NLM ID
0370623
PMCID
PMC2914489
Subset
IM
Grants
NIDA NIH HHS · R01 DA020032 · United States
NIDA NIH HHS · DA020032 · United States
NIDA NIH HHS · DA026434 · United States
External Links
PubMed source DOI: 10.1021/bi100686t PMC Full Text View journal details
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