Abstract
Thymosin α1 is a peptidic hormone already used in the therapy of several diseases. Until now, the description of the precise receptor and mechanism for its action still remains elusive. The interaction of Thymosin α1, which is unstructured in water solution, has been recently studied in sodium dodecylsulphate micellar systems and it was reported that Thymosin α1 inserts in micelle assuming a conformation with two tracts of helix with a structural break in between. An investigation of its interaction both with micelles of dodecylphosphocholine alone and with mixed dodecylphosphocholine-sodium dodecylsulphate micelles is here reported. In these environments the results indicate that Thymosin α1 in phospholipidic membrane exposing choline polar heads interacts by aspecific modality and, oppositely, in the mixed dodecylphosphocholine-sodium dodecylsulphate micelles an insertion in the micellar hydrophobic region conformationally similar to that found in sodium dodecylsulphate micelles occurs. In presence of mixed micelles the insertion and structuration occur in preferred regions when the membrane models are negatively charged. From the point of view of the mechanism of action, insertion its N terminus in negative regions of membrane led to hypothesize that this process would be similar to a binding to phosphatidylserine exposed like in apoptotic cells. Thymosin α1 when inserted may interact with nearby proteins and/or receptors acting as effector and causing a biological signaling cascade. The recent attention to the phosphatidylserine exposure in cells may enforce the interest for these findings.
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Abbreviations
- TFE:
-
Trifluoroethanol
- TSP:
-
Trimethylsilyl propionic acid sodium salt
- DC:
-
Dendritic cell
- SDS:
-
Sodium dodecyl sulfate
- DPC:
-
Dodecylphosphocholine
- Cmc:
-
Critical micellar concentration
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The technical assistance of Fabio Bertocchi in NMR instrumentations mantainance is gratefully acknowledged.
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Handling Editor: M. S. Palma.
W. Mandaliti and R. Nepravishta equally contributed to this work.
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Mandaliti, W., Nepravishta, R., Vallebona, P.S. et al. New studies about the insertion mechanism of Thymosin α1 in negative regions of model membranes as starting point of the bioactivity. Amino Acids 48, 1231–1239 (2016). https://doi.org/10.1007/s00726-016-2169-4
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DOI: https://doi.org/10.1007/s00726-016-2169-4