GPCRs (G-protein-coupled receptors) are versatile signalling molecules at the cell surface and make up the largest and most diverse family of membrane receptors in the human genome. They convert a large variety of extracellular stimuli into intracellular responses through the activation of heterotrimeric G-proteins, which make them key regulatory elements in a broad range of normal and pathological processes, and are therefore one of the most important targets for pharmaceutical drug discovery. Knowledge of a GPCR structure enables us to gain a mechanistic insight into its function and dynamics, and further aid rational drug design. Despite intensive research carried out over the last three decades, resolving the structural basis of GPCR function is still a major activity. The crystal structures obtained in the last 5 years provide the first opportunity to understand how protein structure dictates the unique functional properties of these complex signalling molecules. However, owing to the intrinsic hydrophobicity, flexibility and instability of membrane proteins, it is still a challenge to crystallize GPCRs, and, when this is possible, it is no longer in its native membrane environment and no longer without modification. Furthermore, the conformational change of the transmembrane α-helices associated with the structure activation increases the difficulty of capturing the activation state of a GPCR to a higher resolution by X-ray crystallography. On the other hand, solid-state NMR may offer a unique opportunity to study membrane protein structure, ligand binding and activation at atomic resolution in the native membrane environment, as well as described functionally significant dynamics. In the present review, we discuss some recent achievements of solid-state NMR for understanding GPCRs, the largest mammalian proteome at ~1% of the total expressed proteins. Structural information, details of determination, details of ligand conformations and the consequences of ligand binding to initiate activation can all be explored with solid-state NMR.

In this study, we described the chain order change of binary unsaturated lipid bilayers by studying pure 2-oleoyl-1-pamlitoyl-sn-glyecro-3-phosphocholine (POPC) bilayers, 2-oleoyl-1-pamlitoyl-sn-glyecro-3-glycerol (POPG) bilayers, and POPC/POPG bilayers. The interactions between the POPC/POPG membrane and three model peptides containing basic, aromatic, and hydrophobic residues were studied to investigate the effects of the peptide orientation on the acyl chain order of the POPC/POPG bilayers. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopic studies showed that the acyl chain order of the POPC/POPG bilayers decreased as compared to that of the pure POPC or POPG bilayers. The chain order of the POPC/POPG bilayers significantly decreased when Gravin was added as compared to that when Vamp2 or Antp was added. Fluorescence spectroscopic measurements further show that the tryptophan of the three peptides may interact with the hydrophobic region of the POPC/POPG bilayers, thus resulting in a change in the conformational order of the POPC/POPG acyl chains. This study may provide valuable insight into the dynamics and flexibility of lipid bilayers with different lipids and highlights the importance of aromatic residues in peptide binding to the membrane.