title: Thymosin α1 Interacts with Exposed Phosphatidylserine in Membrane Models and in Cells and Uses Serum Albumin as a Carrier.
abstract: Thymosin α1 is a peptidic hormone with pleiotropic activity and is used in the therapy of several diseases. It is unstructured in water solution and interacts with negative regions of vesicles by assuming two tracts of helical conformation with a structural break between them. This study reports on Thymosin α1's interaction with mixed phospholipids phosphatidylcholine and phosphatidylserine, the negative component of the membranes, by ¹H and natural abundance ¹⁵N nuclear magnetic resonance (NMR). The results indicate that interaction occurs when the membrane is negatively charged by exposing phosphatidylserine. Moreover, the direct interaction of Thymosin α1 with K562 cells with an overexposure of phosphatidylserine as a consequence of resveratrol-induced apoptosis was conducted. Thymosin α1's interaction with human serum albumin was also investigated by NMR spectroscopy. Steady-state saturation transfer, transfer nuclear Overhauser effect spectroscopy, and diffusion-ordered spectroscopy methodologies all reveal that the C-terminal region of Thymosin α1 is involved in the interaction with serum albumin. These results may shed more light on Thymosin α1's mechanism of action by its insertion in negative regions of membranes due to the exposure of phosphatidylserine. Once Thymosin α1's N-terminus has been inserted into the membrane, the rest may interact with nearby proteins and/or receptors acting as effectors and causing a biological signaling cascade, thus exerting thymosin α1's pleiotropy.
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata" , Via della Ricerca Scientifica 1, 00133 Rome, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Mandaliti
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata" , Via della Ricerca Scientifica 1, 00133 Rome, Italy.|Department of Chemical Pharmaceutical and Biomolecular Technologies, Faculty of Pharmacy Catholic University "Our Lady of Good Counsel" , Rr. D. Hoxha, Tirane, Albania.
authors.forename: Ridvan
authors.initials: R
authors.lastname: Nepravishta
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata" , Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sinibaldi Vallebona
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata" , Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pica
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata" , Via Montpellier 1, 00133 Rome, Italy.|San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care , 00163 Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata" , Via della Ricerca Scientifica 1, 00133 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Paci
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D010718:Phosphatidylserines; D012709:Serum Albumin; D013947:Thymosin; D000077596:Thymalfasin