Journal of Biomolecular NMR

, Volume 65, Issue 1, pp 1–5 | Cite as

Ring current shifts in 19F-NMR of membrane proteins



Fluorine-19 NMR markers are attractive reporter groups for use in studies of complex biomacromolecular systems, in particular also for studies of function-related conformational equilibria and rate processes in membrane proteins. Advantages of 19F-NMR probes include high sensitivity of the 19F chemical shifts to variations in the non-covalent environment. Nonetheless, in studies of G protein-coupled receptors (GPCR) we encountered situations where 19F chemical shifts were not responsive to conformational changes that had been implicated by other methods. This prompted us to examine possible effects of aromatic ring current fields on the chemical shifts of 19F-NMR probes used in GPCRs. Analysis of previously reported 19F-NMR data on the β2-adrenergic receptor and mammalian rhodopsin showed that all 19F-labeling sites which manifested conformational changes are located near aromatic residues. Although ring current effects are small when compared to other known non-covalent effects on 19F chemical shifts, there is thus an indication that their contributions are significant when studying activation processes in GPCRs, since the observed activation-related 19F-NMR chemical shifts are comparable in size to the calculated ring current shifts. Considering the impact of ring current shifts may thus be helpful in identifying promising indigenous or engineered labeling sites for future 19F-NMR studies of GPCR activation, and novel information may be obtained on the nature of conformational rearrangements near the 19F-labels. It will then also be interesting to see if the presently indicated role of ring current shifts in membrane protein studies with 19F-NMR markers can be substantiated by a more extensive data base resulting from future studies.


G-protein coupled receptors 19F-NMR probes Chemical modification of cysteines Membrane protein functional studies 



The authors acknowledge financial support by the ShanghaiTech University, the Shanghai Municipal Government, and the “Users with Excellence” Project (2015HSC-UE012) of the Hefei Science Center, the Chinese Academy of Sciences. We thank Ms. Ya Yuan for a careful reading of the manuscript.


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.iHuman InstituteShanghaiTech UniversityShanghaiChina
  2. 2.Department of Integrative Structural and Computational Biology, and The Skaggs Institute for Chemical BiologyThe Scripps Research InstituteLa JollaUSA

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