guest ::
| Home > Publications database > Structural heterogeneity of the $μ$-opioid receptor’s conformational ensemble in the apo state |
| Home > Publications database > Structural heterogeneity of the $μ$-opioid receptor’s conformational ensemble in the apo state |
| Journal Article | FZJ-2017-03089 |
; ; ; ;
2017
Nature Publishing Group
London
This record in other databases: 
Please use a persistent id in citations: http://hdl.handle.net/2128/14205 doi:10.1038/srep45761
Abstract: G-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W2936.48 at the “toggle switch” in the mutation-induced constitutive activation. Such role has been already observed for other CAMs of class A GPCRs. We also find a significantly populated intermediate state, rather similar to IS. Based on the remarkable accord between simulations and experiments, we suggest here that this state, which has escaped so far experimental characterization, might constitute an early step in the activation process of the apo μOR CAM.
; 
; 
; 
; BIOSIS Previews ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record
|
The record appears in these collections: |
PDF
PDF (PDFA)