Mandaliti Walter, Nepravishta Ridvan, Sinibaldi Vallebona Paola, Pica Francesca, Garaci Enrico, Paci Maurizio
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.
Biochemistry. 2016 Mar 15;55(10):1462-72. doi: 10.1021/acs.biochem.5b01345. Epub 2016 Mar 3.
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.
胸腺素α1是一种具有多效活性的肽类激素，用于多种疾病的治疗。它在水溶液中无特定结构，通过形成两段螺旋构象并在其间存在结构断点的方式与囊泡的负电区域相互作用。本研究通过¹H和天然丰度¹⁵N核磁共振（NMR）报告了胸腺素α1与混合磷脂磷脂酰胆碱和膜的负性成分磷脂酰丝氨酸的相互作用。结果表明，当膜因暴露磷脂酰丝氨酸而带负电时会发生相互作用。此外，还进行了胸腺素α1与因白藜芦醇诱导凋亡而过度暴露磷脂酰丝氨酸的K562细胞的直接相互作用研究。还通过核磁共振光谱研究了胸腺素α1与人血清白蛋白的相互作用。稳态饱和转移、转移核Overhauser效应光谱和扩散排序光谱方法均表明，胸腺素α1的C末端区域参与了与血清白蛋白的相互作用。这些结果可能通过胸腺素α1因磷脂酰丝氨酸暴露而插入膜的负性区域来更深入地揭示其作用机制。一旦胸腺素α1的N末端插入膜中，其余部分可能与附近的蛋白质和/或受体相互作用，充当效应器并引发生物信号级联反应，从而发挥胸腺素α1的多效性。
