Proton transfer during class-A GPCR activation: do the CWxP motif and the membrane potential act in concert?
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摘要:
INTRODUCTION
G-protein-coupled receptors (GPCRs) form the largest receptor superfamily of eukaryotic cells (Flock et al.2017).A typical GPCR protein contains seven transmembrane helices (TMs 1-7) (Palczewski et al.2000).Upon activation,the GPCR opens a cavity on its cytoplasmic side,between TMs 5-6 and the remaining of the receptor,to interact with downstream effectors such as G-proteins and arrestins (Kang et al.2015;Rasmussen et al.2011).Based on phylogenetic analysis,GPCRs have been further categorized into several families.Among them,the rhodopsin-like class-A—referred to as such in the A-F classification system (Attwood and Findlay 1994;Kolakowski 1994)—is the largest family,including over 700 members from human genome alone.