Abstract
In this study we investigated the dynamic behavior of the chimeric cell-penetrating peptide transportan in membrane-like environments using NMR. Backbone amide 15N spin relaxation was used to investigate the dynamics in two bicelles: neutral DMPC bicelles and partly negatively charged DMPG-containing bicelles. The structure of the peptide as judged from CD and chemical shifts is similar in the two cases. Both the overall motion as well as the local dynamics is, however, different in the two types of bicelles. The overall dynamics of the peptide is significantly slower in the partly negatively charged bicelle environment, as evidenced by longer global correlation times for all measured sites. The local motion, as judged from generalized order parameters, is for all sites in the peptide more restricted when bound to negatively charged bicelles than when bound to neutral bicelles (increase in S 2 is on average 0.11 ± 0.07). The slower dynamics of transportan in charged membrane model systems cause significant line broadening in the proton NMR spectrum, which in certain cases limits the observation of 1H signals for transportan when bound to the membrane. The effect of transportan on DMPC and DHPC motion in zwitterionic bicelles was also investigated, and the motion of both components in the bicelle was found to be affected.
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Abbreviations
- CPMG:
-
Carr-Purcell-Meiboom-Gill
- CPP:
-
cell-penetrating peptide
- DHPC:
-
1,2-dihexanoyl-sn-glycero-3-phosphocholine
- DHPC-d 22 :
-
deuterated 1,2-dihexanoyl-sn-glycero-3-phosphocholine
- DMPC:
-
1,2-dimyristoyl-sn-glycero-3-phosphocholine
- DMPC-d 54 :
-
deuterated 1,2-dimyristoyl-sn-glycero-3-phosphocholine
- DMPG-d 54 :
-
deuterated 1,2-dimyrisotoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]
- HSQC:
-
heteronuclear single quantum coherence
- NMR:
-
nuclear magnetic resonance
- NOE:
-
nuclear Overhauser enhancement
- PNAs:
-
peptide nucleic acids
- siRNA:
-
small interfering RNA
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Acknowledgements
We wish to thank Joshua Hicks for helpful insights and careful reading of the manuscript. This work is supported by grants from the Swedish Research Council and the Carl Trygger Foundation.
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Bárány-Wallje, E., Andersson, A., Gräslund, A. et al. Dynamics of transportan in bicelles is surface charge dependent. J Biomol NMR 35, 137–147 (2006). https://doi.org/10.1007/s10858-006-9008-y
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DOI: https://doi.org/10.1007/s10858-006-9008-y