Zinc Coordination by Thymosin β4: Structural Determinants and Functional Implications.

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Thymosin β4 (Tβ4) is a peptide with diverse biological roles.
• Its interactions with metal ions, particularly Zn²⁺, are not well understood.
• Understanding these interactions is crucial for elucidating Tβ4's function.

Purpose of the Study:

• To investigate the interaction between Thymosin β4 (Tβ4) and Zn²⁺ ions.
• To determine if Zn²⁺ binding induces structural changes or aggregation in Tβ4.
• To assess the physiological relevance of Tβ4/Zn²⁺ interactions.

Main Methods:

• Zeta potential analysis
• Dynamic light scattering (DLS)
• Electrospray ionization mass spectrometry (ESI-MS)
• Nuclear magnetic resonance (NMR) spectroscopy
• Scanning electron microscopy with elemental mapping (SEM/EDS)

Main Results:

• Tβ4 forms discrete Zn²⁺-bound adducts and aggregates under physiological pH.
• Zn(II) binding neutralizes Tβ4's negative charge, triggering aggregation.
• ESI-MS identified Tβ4/Zn(II) complexes with a 1:3 molar ratio; DLS and SEM showed compact assemblies.
• NMR confirmed Zn(II)-induced aggregation without Tβ4 folding.

Conclusions:

• Zn(II)-induced aggregation of Tβ4 is feasible in zinc-rich microdomains (e.g., synaptic cleft), but unlikely in plasma.
• This Zn(II)-mediated supramolecular assembly could influence Tβ4 behavior in neurological and inflammatory conditions.
• Establishes a biochemical framework for studying Tβ4/Zn(II) complexation in vivo.